Phenotypes associated with this allele

• Allele Symbol: Speer6-ps1⁺
• Allele Name: wild type
• Allele ID: MGI:6157292
• Summary: 232 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Adh5^tm1.1Llli/Adh5^tm1.1Llli Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Adh5^tm1.1Llli Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:5049927
cn2	Ahr^tm3.1Bra/Ahr^tm3.1Bra Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Ahr^tm3.1Bra Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:3613531
cn3	Dhcr24^tm1c(EUCOMM)Wtsi/Dhcr24^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Dhcr24^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:6715351
cn4	Dhcr7^tm1.1Sbpa/Dhcr7^tm1.1Sbpa Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Dhcr7^tm1.1Sbpa Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:6690698
cn5	Ggcx^tm1Sinos/Ggcx^tm1Sinos Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Ggcx^tm1Sinos Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:5662240
cn6	Ggcx^tm1Sinos/Ggcx^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Ggcx^tm1Sinos Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:5662241
cn7	Hmgcl^tm2Gam/Hmgcl^tm2Gam Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Hmgcl^tm2Gam Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:5538628
cn8	Hs2st1^tm1.1Je/Hs2st1^tm1.1Je Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Hs2st1^tm1.1Je Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:4439271
cn9	Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^Gt(CC0690)Wtsi/Mob1b^Gt(CC0690)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Mob1b^Gt(CC0690)Wtsi Mob1a^tm1.1Asuz Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:5897809
cn10	Scarb1^tm1Thh/Scarb1^tm1Thh Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Scarb1^tm1Thh Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:3697677
cn11	Ahr^b-1/Ahr^b-1 Aip^tm2.1Bra/Aip^tm2.1Bra Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Speer6-ps1^Tg(Alb-cre)21Mgn Aip^tm2.1Bra	MGI:4867849
cn12	Naa40^tm1Qwzh/Naa40^tm1Qwzh Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Speer6-ps1^Tg(Alb-cre)21Mgn Naa40^tm1Qwzh	MGI:5317915
cn13	Rubcnl^em1Qsun/Rubcnl^em1Qsun Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Speer6-ps1^Tg(Alb-cre)21Mgn Rubcnl^em1Qsun	MGI:6361078
cn14	Scd1^tm2Ntam/Scd1^tm2Ntam Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Speer6-ps1^Tg(Alb-cre)21Mgn Scd1^tm2Ntam	MGI:3773310
cn15	Ssu72^tm1Cwl/Ssu72^tm1Cwl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	B6.Cg-Ssu72^tm1Cwl Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:7384742
cn16	Abcb7^tm1Mdf/Y Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	either: B6.Cg-Speer6-ps1^Tg(Alb-cre)21Mgn Abcb7^tm1Mdf or (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * DBA)	MGI:3629066
cn17	Cav1^tm1Pesch/Cav1^tm1Pesch Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	FVB.Cg-Cav1^tm1Pesch Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:5316849
cn18	Stk3^tm1Jav/Stk3^tm1Jav Stk4^Gt(AJ0315)Wtsi/Stk4^Gt(AJ0315)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * 129P2/OlaHsd * C57BL/6 * DBA	MGI:5824005
cn19	Arnt^tm1Bra/Arnt^tm1Bra Vhl^tm1Jae/Vhl^tm1Jae Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * BALB/c * C57BL/6 * DBA	MGI:3621473
cn20	Hif1a^tm3Rsjo/Hif1a^tm3Rsjo Vhl^tm1Jae/Vhl^tm1Jae Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * BALB/c * C57BL/6 * DBA	MGI:3621471
cn21	Stk3^tm1Jav/Stk3^tm1Jav Stk4^Gt(AJ0315)Wtsi/Stk4^Gt(AJ0315)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6	MGI:4411991
cn22	Wwc1^tm1Arsc/Wwc1^tm1Arsc Wwc2^tm1.1Arte/Wwc2^tm1.1Arte Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * C57BL/6J * DBA	MGI:6711445
cn23	Gfer^tm1.1Crg/Gfer^tm1.1Crg Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * DBA	MGI:5762654
cn24	Mia2^tm1Zhxu/Mia2^tm1Zhxu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * DBA	MGI:6358148
cn25	Ppargc1a^tm2Brsp/Ppargc1a^tm2Brsp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * DBA	MGI:3694896
cn26	Hif1an^tm1.1Rsjo/Hif1an^tm1.1Rsjo Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * DBA	MGI:4459910
cn27	Cdk1^tm2.1Kald/Cdk1^tm2.1Kald Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * DBA * SJL	MGI:5318109
cn28	Nr1h3^tm1Djm/Nr1h3^tm1Djm Nus1^tm1.1Qrm/Nus1^tm1.1Qrm Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * DBA * SJL	MGI:6106901
cn29	Nus1^tm1.1Qrm/Nus1^tm1.1Qrm Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129 * C57BL/6 * DBA * SJL	MGI:6106900
cn30	Ptpn11^tm1Gsf/Ptpn11^tm1Gsf Stat3^tm1Vpo/Stat3^tm1Vpo Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:5009547
cn31	Ccn2^tm1.1Alea/Ccn2^tm1.1Alea Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^Gt(CC0690)Wtsi/Mob1b^Gt(CC0690)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * DBA	MGI:5897813
cn32	Kras^tm4Tyj/Kras^tm4Tyj Yap1^tm1.1Dupa/Yap1^tm1.1Dupa Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:4819844
cn33	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:5428898
cn34	Irs1^tm2Tka/Irs1^tm2Tka Irs2^tm2Tka/Irs2^tm2Tka Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:3805348
cn35	Akt2^tm1.1Mbb/Akt2^tm1.1Mbb Pten^tm1Hwu/Pten^tm1Hwu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:4838529
cn36	Kras^tm4Tyj/Kras^+ Pten^tm2Mak/Pten^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:6256732
cn37	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:5428907
cn38	Kras^tm4Tyj/Kras^+ Pten^tm2Mak/Pten^tm2Mak Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:6256730
cn39	Atp8b1^tm1Nbf/Atp8b1^tm1Nbf Por^tm1Wolf/Por^tm1Wolf Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:5618808
cn40	Met^tm1Sst/Met^tm1Sst Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3041261
cn41	Pten^tm2Mak/Pten^tm2Mak Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * DBA	MGI:5702658
cn42	Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^Gt(CC0690)Wtsi/Mob1b^Gt(CC0690)Wtsi Yap1^tm1c(KOMP)Mbp/Yap1^tm1c(KOMP)Mbp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * DBA	MGI:5897815
cn43	Foxa2^tm1Khk/Foxa2^tm1Khk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA	MGI:2177363
cn44	Irs1^tm2Tka/Irs1^tm2Tka Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:3805350
cn45	Acsl1^tm1Rcol/Acsl1^tm1Rcol Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4417849
cn46	Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^Gt(CC0690)Wtsi/Mob1b^Gt(CC0690)Wtsi Wwtr1^tm1Hku/Wwtr1^tm1Hku Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5897811
cn47	Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^Gt(CC0690)Wtsi/Mob1b^Gt(CC0690)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tgfbr2^tm1Roes/Tgfbr2^tm1Roes	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5897816
cn48	Apoe^tm1Unc/Apoe^tm1Unc Smarcd1^tm1.1Jddl/Smarcd1^tm1.1Jddl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5912277
cn49	Hmgb1^tm1.1Ttg/Hmgb1^tm1.1Ttg Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5563542
cn50	Yap1^tm1.1Dupa/Yap1^tm1.1Dupa Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4819841
cn51	Nf2^tm2Gth/Nf2^tm2Gth Yap1^tm1.1Dupa/Yap1^tm1.1Dupa Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4819842
cn52	Nf2^tm2Gth/Nf2^tm2Gth Yap1^tm1.1Dupa/Yap1^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4819843
cn53	Nf2^tm2Gth/Nf2^tm2Gth Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4819845
cn54	Cyb5a^tm1Wolf/Cyb5a^tm1Wolf Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:3826674
cn55	Hsd11b1^tm1Ggla/Hsd11b1^tm1Ggla Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5444453
cn56	Keap1^tm1Mym/Keap1^tm2Mym Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:3620636
cn57	Rr27^tm2Msb/Rr27^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:3620114
cn58	Pten^tm2Mak/Pten^tm2Mak Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:3806986
cn59	Stat3^tm1Vpo/Stat3^tm1Vpo Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5009548
cn60	Map3k7^tm1Aki/Map3k7^tm1Aki Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:4461042
cn61	Por^tm2Wolf/Por^tm1Wolf Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:2656921
cn62	Por^tm1Wolf/Por^tm1Wolf Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:2656922
cn63	Abcb4^tm1Bor/Abcb4^tm1Bor Por^tm1Wolf/Por^tm1Wolf Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA * FVB/N	MGI:5618809
cn64	Abhd5^tm1.1Lqyu/Abhd5^tm1.1Lqyu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * DBA	MGI:5523090
cn65	Gab1^tm1Gsf/Gab1^tm1Gsf Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3578950
cn66	Pdss2^tm1Dalg/Pdss2^tm1Dalg Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3805708
cn67	Ptpn11^tm1Gsf/Ptpn11^tm1Gsf Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:5009546
cn68	Ei24^tm1Hzha/Ei24^tm1Hzha Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:5475096
cn69	Pex5^tm1Pec/Pex5^tm1Pec Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3851810
cn70	Irs1^tm1Mfw/Irs1^tm1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3805306
cn71	Adar^tm1Knk/Adar^tm1Knk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3032498
cn72	Ndst1^tm1Je/Ndst1^tm1Je Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:4439272
cn73	Mtch2^tm2Atgr/Mtch2^tm2.1Atgr Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:5566667
cn74	Irs1^tm1Mfw/Irs1^tm1Mfw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3805308
cn75	Ern1^tm1Rjk/Ern1^tm2.1Rjk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:4949418
cn76	Mir122^tm1.2Kgh/Mir122^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:5448536
cn77	Mir122^tm1.2Kgh/Mir122^tm1.2Kgh Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:5448537
cn78	Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3805307
cn79	Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(tetO-Xbp1_is)#Pesch/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB	MGI:6376140
cn80	Foxo1^tm1Rdp/Foxo1^tm1Rdp Irs1^tm1Mfw/Irs1^tm1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB	MGI:3805304
cn81	Irs1^tm1Mfw/Irs1^+ Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N	MGI:4430357
cn82	Irs1^tm2.1Mfw/Irs1^tm2.1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N	MGI:4430358
cn83	Irs1^tm1Mfw/Irs1^tm2.1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N	MGI:4430356
cn84	Notch2^tm3Grid/Notch2^tm3.1Grid Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * C57BL/6 * DBA	MGI:3778811
cn85	Por^tm1Ding/Por^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * C57BL/6 * DBA	MGI:3704087
cn86	Aqp11^tm1.1Nlsn/Aqp11^tm1.1Nlsn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * C57BL/6 * DBA	MGI:5485021
cn87	Por^tm1Ding/Por^tm1Ding Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * C57BL/6 * DBA	MGI:2668453
cn88	Notch2^tm2Grid/Notch2^tm3Grid Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * C57BL/6 * DBA	MGI:3778812
cn89	Foxo1^tm1Rdp/Foxo1^tm1Rdp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * C57BL/6 * DBA * FVB	MGI:3805303
cn90	Pros1^tm1Grl/Pros1^tm1Grl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/SvImJ * C57BL/6 * DBA	MGI:5499118
cn91	Polr2m^tm1.1Rgr/Polr2m^tm1.1Rgr Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6 * DBA	MGI:6515760
cn92	Ncor1^tm1Anh/Ncor1^tm1Anh Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6 * DBA	MGI:3821875
cn93	Vhl^tm1Jae/Vhl^tm1Jae Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA	MGI:2176966
cn94	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * C57BL/6J	MGI:6791351
cn95	Pnpla2^tm1Gam/Pnpla2^tm1Gam Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * DBA	MGI:5427456
cn96	Fbxw7^tm1Iken/Fbxw7^tm1Iken Kras^tm4Tyj/Kras^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * C57BL/6N * DBA	MGI:6157296
cn97	Fbxw7^tm1Iken/Fbxw7^+ Kras^tm4Tyj/Kras^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * C57BL/6N * DBA	MGI:6157295
cn98	Kras^tm4Tyj/Kras^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:5428897
cn99	Vhl^tm1Jae/Vhl^tm1Jae Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:3832405
cn100	Pten^tm1Hwu/Pten^tm1Hwu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:4829790
cn101	Irs2^tm2Tka/Irs2^tm2Tka Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:3805349
cn102	Ccn1^tm3.1Lfl/Ccn1^tm3.1Lfl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:5529807
cn103	Rraga^tm2Dmsa/Rraga^tm2Dmsa Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:6236292
cn104	Tsc1^tm1Djk/Tsc1^tm1Djk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:5009705
cn105	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3775382
cn106	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3775385
cn107	Insr^tm1Khn/Insr^tm1Khn Pdx1^tm1Ted/Pdx1^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3583116
cn108	Ptpn1^tm2Bbk/Ptpn1^tm2Bbk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3664093
cn109	Gt(ROSA)26Sor^tm2(sb11)Njen/Gt(ROSA)26Sor^+ Trp53^tm3Tyj/Trp53^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ TgTn(sb-T2/Onc)68Dla/0	involves: 129S4/SvJae * C57BL/6 * DBA/2 * FVB/N	MGI:3839859
cn110	Sephs1^tm1.1Dhat/Sephs1^tm1.1Dhat Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6J	MGI:6189551
cn111	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL/6J * DBA/2 * FVB	MGI:3039262
cn112	Zbtb20^tm1Wpjz/Zbtb20^tm1Wpjz Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJae * C57BL * C57BL/6 * DBA	MGI:3812018
cn113	Ghr^tm1.1Masp/Ghr^tm1.1Masp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJaeSor * C57BL/6 * DBA	MGI:4359908
cn114	Cdk5rap3^tm1c(EUCOMM)Hmgu/Cdk5rap3^tm1c(EUCOMM)Hmgu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S4/SvJaeSor * C57BL/6N * DBA	MGI:6295913
cn115	Pck1^tm1.1Mgn/Pck1^tm1.1Mgn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac	MGI:3029211
cn116	Abca1^tm1Jp/Abca1^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * B6.Cg-Tg(Alb-cre)21Mgn/J	MGI:3578114
cn117	Abca1^tm1Jp/Abca1^tm1Jp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * B6.Cg-Tg(Alb-cre)21Mgn/J	MGI:3578113
cn118	Gt(ROSA)26Sor^tm3(HIF1A*)Kael/Gt(ROSA)26Sor^tm4(HIF2A*)Kael Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA	MGI:3832404
cn119	Gt(ROSA)26Sor^tm3(HIF1A*)Kael/Gt(ROSA)26Sor^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA	MGI:3832402
cn120	Gt(ROSA)26Sor^tm4(HIF2A*)Kael/Gt(ROSA)26Sor^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA	MGI:3832403
cn121	Hjv^tm1Kpan/Hjv^tm1Kpan Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6	MGI:5792902
cn122	Lamp2^tm1Amcu/Y Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J	MGI:5691397
cn123	Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * C57BL/6NTac	MGI:6791347
cn124	Tor1a^tm3.1Wtd/Tor1a^tm3.1Wtd Tor1aip1^tm1.1Wtd/Tor1aip1^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA	MGI:7611650
cn125	Il7^tm2.1Iku/Il7^tm2.1Iku Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA	MGI:5461227
cn126	Tor1a^tm3.1Wtd/Tor1a^tm3.1Wtd Tor1aip1^tm1.1Wtd/Tor1aip1^tm1.1Wtd Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA	MGI:7611647
cn127	Tor1a^tm3.1Wtd/Tor1a^tm3.1Wtd Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA	MGI:7611649
cn128	Gys2^tm1.1Pro/Gys2^tm1.1Pro Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA	MGI:4462847
cn129	Tor1a^tm3.1Wtd/Tor1a^+ Tor1aip1^tm1.1Wtd/Tor1aip1^tm1.1Wtd Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA	MGI:7611653
cn130	Tjp1^tm1.1Whun/Tjp1^tm1.1Whun Tjp2^tm2Whun/Tjp2^tm2Whun Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2	MGI:6719082
cn131	Tjp2^tm2Whun/Tjp2^tm2Whun Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac * DBA/2	MGI:6719086
cn132	Sav1^tm1.1Rjo/Sav1^tm1.1Rjo Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * CD-1 * DBA * SJL	MGI:4430548
cn133	Stk3^tm1.1Rjo/Stk3^tm1.1Rjo Stk4^tm1.1Rjo/Stk4^tm1.1Rjo Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * CD-1 * DBA * SJL	MGI:4430567
cn134	Gclc^tm1Tdal/Gclc^tm1Tdal Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:5519060
cn135	Gak^tm2Legr/Gak^tm2Legr Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:5305778
cn136	Hdac3^tm1Swh/Hdac3^tm1.1Swh Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3795939
cn137	Hs6st1^tm1Wvc/Hs6st1^tm1Wvc Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:4439273
cn138	Abca1^tm1Jp/Abca1^tm1Jp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:4358982
cn139	Gck^tm1.1Mgn/Gck^tm1.1Mgn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:3603013
cn140	Chrm3^tm2.1Jwe/Chrm3^tm2.1Jwe Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA * FVB/N	MGI:4438748
cn141	Abca1^tm1Jp/Abca1^tm1Jp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(Vil1-cre)997Gum/0	involves: 129S6/SvEvTac * C57BL/6 * DBA * SJL	MGI:4358977
cn142	Bub1b^tm1Jvd/Bub1b^tm1Jvd Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * FVB	MGI:6791353
cn143	Coq7^tm1Hek/Coq7^tm2Hek Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6NTac	MGI:5532534
cn144	Acaca^tm2Sjw/Acaca^tm2Sjw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S7/SvEvBrd * C57BL/6J * FVB	MGI:3641135
cn145	Soat2^tm1.1Llr/Soat2^tm1.1Llr Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * DBA	MGI:5426955
cn146	Nr5a2^tm1Sakl/Nr5a2^tm1Sakl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * DBA	MGI:3797770
cn147	Tmem30a^tm1.1Xjz/Tmem30a^tm1.1Xjz Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6J * DBA	MGI:6119462
cn148	Ldlr^tm1Her/Ldlr^tm1Her Nr1h3^tm1.1Djm/Nr1h3^tm1.1Djm Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * DBA	MGI:5427004
cn149	Nr0b2^tm1Mjev/Nr0b2^tm1Mjev Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEvBrd * C57BL/6 * DBA	MGI:3847955
cn150	Rptor^tm1.1Dmsa/Rptor^tm1.1Dmsa Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEv * C57BL/6 * DBA	MGI:4879104
cn151	Nr1h3^tm1.1Djm/Nr1h3^tm1.1Djm Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEv * C57BL/6 * DBA	MGI:5427002
cn152	Commd1^tm2.1Bvds/Commd1^tm2.1Bvds Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S/SvEv * C57BL/6 * DBA * SJL	MGI:5315714
cn153	Smad2^tm1.1Epb/Smad2^tm1.1Epb Smad3^tm1Cxd/Smad3^tm1Cxd Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * DBA * SJL	MGI:3703883
cn154	Ldlr^tm1Her/Ldlr^tm1Her Nr5a2^tm1Sjns/Nr5a2^tm1Sjns Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * DBA	MGI:5607406
cn155	Igf2r^tm1Rlj/Igf2r^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129/Sv * C57BL/6 * DBA	MGI:3795373
cn156	Smad2^tm1.1Epb/Smad2^tm1.1Epb Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129/Sv * C57BL/6 * DBA * SJL	MGI:3703880
cn157	Ptpn11^tm3Bgn/Ptpn11^tm3Bgn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129X1/SvJ * C57BL/6 * C57BL/6J * DBA	MGI:4868455
cn158	Foxm1^tm1Rhc/Foxm1^tm1Rhc Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129X1/SvJ * C57BL/6 * DBA	MGI:3522661
cn159	Prkaca^tm3Gsm/Prkaca^tm3Gsm Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129X1/SvJ * C57BL/6J	MGI:3615115
cn160	Nfe2l1^tm1Jefc/Nfe2l1^tm1Ywk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129X1/SvJ * C57BL/6J	MGI:3575312
cn161	Srsf3^tm1Pjln/Srsf3^tm1Pjln Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: BALB/c * C57BL/6 * DBA	MGI:5605688
cn162	Cluh^tm1.1Eir/Cluh^tm1.1Eir Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: BALB/cJ * C57BL/6 * DBA * SJL	MGI:6119620
cn163	Lman1^tm1c(KOMP)Wtsi/Lman1^tm1c(KOMP)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * C57BL/6N	MGI:5607591
cn164	Mpc1^tm1c(EUCOMM)Wtsi/Mpc1^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA	MGI:5903311
cn165	Thrap3^tm1c(KOMP)Wtsi/Thrap3^tm1c(KOMP)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA	MGI:7531058
cn166	Hmox1^tm1.1Hes/Hmox1^tm1.1Hes Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA	MGI:5660646
cn167	Glul^tm1.1Geno/Glul^tm1.1Geno Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * DBA	MGI:5758759
cn168	Bmal1^tm1.1Shbi/Bmal1^tm1.1Shbi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * DBA	MGI:5613394
cn169	Sirt3^tm1.1Auw/Sirt3^tm1.1Auw Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * DBA	MGI:5556080
cn170	Tor1aip2^tm1.1Wtd/Tor1aip2^tm1.1Wtd Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * DBA	MGI:7611637
cn171	Pik3c3^tm1c(EUCOMM)Wtsi/Pik3c3^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(CAG-EGFP/Map1lc3b)53Nmz/0	involves: C57BL/6 * C57BL/6N * C57BL/6NCrj * DBA	MGI:5427446
cn172	Tjp1^tm1.1Whun/Tjp1^tm1.1Whun Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2	MGI:6719088
cn173	Faf2^tm1Tfji/Faf2^tm1Tfji Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * CBA * DBA	MGI:5805372
cn174	Pik3c3^tm1c(EUCOMM)Wtsi/Pik3c3^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * DBA	MGI:5427443
cn175	Sco1^tm1c(KOMP)Wtsi/Sco1^tm1c(KOMP)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * DBA	MGI:5758892
cn176	Zc3h12a^tm1c(EUCOMM)Hmgu/Zc3h12a^tm1c(EUCOMM)Hmgu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * DBA	MGI:6717173
cn177	Fbxw7^tm1Iken/Fbxw7^tm1Iken Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * DBA	MGI:6157293
cn178	Secisbp2^tm1c(EUCOMM)Wtsi/Secisbp2^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * DBA	MGI:5583958
cn179	Pcx^tm1c(EUCOMM)Wtsi/Pcx^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * DBA * SJL	MGI:7414196
cn180	Il6ra^tm1.1Drew/Il6ra^tm1.1Drew Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * SJL	MGI:4456459
cn181	Lpcat3^tm1c(EUCOMM)Wtsi/Lpcat3^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * SJL	MGI:5822858
cn182	Cul4a^tm1.1Pra/Cul4a^tm1.1Pra Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6NTac * DBA	MGI:5003273
cn183	Psmg1^tm1.1Smta/Psmg1^tm1.1Smta Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * CBA * DBA	MGI:4820736
cn184	Stk3^tm1.1Yy/Stk3^tm1Yy Stk4^tm1.1Yy/Stk4^tm1.1Yy Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * CBA * DBA	MGI:4422187
cn185	Ppdpf^tm1Nju/Ppdpf^tm1Nju Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:6739868
cn186	Pcyt2^tm1.1Suja/Pcyt2^tm1.1Suja Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:4415291
cn187	Polr2m^tm1.1Rgr/Polr2m^tm1.1Rgr Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:6515758
cn188	Cpt2^tm1Mwol/Cpt2^tm1Mwol Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:7407341
cn189	Mir100^em1Nju/Mir100^em1Nju Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:6393588
cn190	Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(CAG-Dusp26)#Jhxia/0	involves: C57BL/6 * DBA	MGI:6361915
cn191	Dusp26^em1Jhxia/Dusp26^em1Jhxia Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:6361914
cn192	Nfe2l1^tm1Mym/Nfe2l1^tm1Mym Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:3828255
cn193	Mirc53^tm1.1Gning/Mirc53^tm1.1Gning Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:6359866
cn194	Txnip^tm1Road/Txnip^tm1Road Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:3809845
cn195	Por^tm3Ding/Por^tm3Ding Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:4457494
cn196	Gpcpd1^tm1c(EUCOMM)Hmgu/Gpcpd1^tm1c(EUCOMM)Hmgu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:7610684
cn197	Sav1^tm2.1Dlim/Sav1^tm2.1Dlim Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:4457497
cn198	Pnpt1^tm1Teit/Pnpt1^tm1Teit Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:4882058
cn199	Derl2^tm1.1Hpl/Derl2^tm1.1Hpl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:4947224
cn200	Ccl2^tm1.1Pame/Ccl2^tm1.1Pame Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:4950282
cn201	Fbxl5^tm2.1Kei/Fbxl5^tm2.1Kei Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5295292
cn202	Cdo1^tm1Mhst/Cdo1^tm1Mhst Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5437229
cn203	Sptlc3^em1Cowl/Sptlc3^em1Cowl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:7858939
cn204	Selenop^tm3.1Rfb/Selenop^tm3.1Rfb Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5466370
cn205	Sqstm1^tm2.1Jmos/Sqstm1^tm2.1Jmos Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5487467
cn206	Creg1^em1Yal/Creg1^em1Yal Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:6196883
cn207	Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Trmu^tm1Tomik/Trmu^tm1Tomik	involves: C57BL/6 * DBA	MGI:6108884
cn208	Gck^tm1Hrt/Gck^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:3618231
cn209	Smarcd1^tm1.1Jddl/Smarcd1^tm1.1Jddl Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5912276
cn210	Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tspo^tm1.1Maf/Tspo^tm1.1Maf	involves: C57BL/6 * DBA	MGI:5588662
cn211	Klf14^tm1.1Yec/Klf14^tm1.1Yec Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5882068
cn212	Trnau1ap^tm2.1Usch/Trnau1ap^tm2.1Usch Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5825445
cn213	Rab30^em1Mwol/Rab30^em1Mwol Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:8210455
cn214	Cpt2^tm1Mwol/Cpt2^tm1Mwol Rab30^em1Mwol/Rab30^em1Mwol Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:8210461
cn215	Ddit3^tm1.1Irt/Ddit3^tm1.1Irt Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(Mup3-Plau)350-2Eps/?	involves: C57BL/6 * DBA	MGI:5781097
cn216	Dio3^tm1Dmst/Dio3^tm1Dmst Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA	MGI:5770122
cn217	Agap2^tm1Kye/Agap2^tm1Kye Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA/2	MGI:5284899
cn218	Uqcc3^em1Hya/Uqcc3^em1Hya Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA/2	MGI:6718327
cn219	Gt(ROSA)26Sor^tm2(sb11)Njen/Gt(ROSA)26Sor^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ TgTn(sb-T2/Onc)68Dla/0	involves: C57BL/6 * DBA/2 * FVB/N	MGI:3839857
cn220	Dbi^tm2.1Smdp/Dbi^tm2.2Smdp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA * FVB/N	MGI:5538740
cn221	Orc1^tm1.1Gle/Orc1^tm1.1Gle Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA * SJL	MGI:6388690
cn222	Orc1^tm1.1Gle/Orc1^tm1.2Gle Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA * SJL	MGI:7408239
cn223	Sec24c^tm1c(EUCOMM)Wtsi/Sec24c^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA * SJL	MGI:5896384
cn224	Gcgr^tm2.1Mjch/Gcgr^tm2.1Mjch Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * DBA * SJL	MGI:5566824
cn225	Blvra^tm1c(EUCOMM)Hmgu/Blvra^tm1c(EUCOMM)Hmgu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6J * C57BL/6N	MGI:5822918
cn226	Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(CAG-cat,-Creg1)#Yal/0	involves: C57BL/6J * DBA	MGI:6196884
cn227	Usp20^em1Gpt/Usp20^em1Gpt Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6JGpt * DBA	MGI:6515651
cn228	Hmgcr^em1Bcgen/Hmgcr^em1Bcgen Usp20^em1Gpt/Usp20^em1Gpt Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6JGpt * DBA	MGI:6515654
cn229	A1cf^tm1c(EUCOMM)Hmgu/A1cf^tm1c(EUCOMM)Hmgu Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6N * DBA	MGI:6384968
cn230	Clk2^tm1.1Ppgr/Clk2^tm1.1Ppgr Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6NTac * FVB/N	MGI:5751747
cn231	Antxr2^tm1.1Lepp/Antxr2^tm1.1Lepp Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * SJL	MGI:4353035
cn232	Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tor1aip1^tm1.1Wtd/Tor1aip1^tm1.1Wtd	Not Specified	MGI:7611657

Genotype
MGI:5049927

cn1

• Allelic Composition: Adh5^tm1.1Llli/Adh5^tm1.1Llli; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Adh5^tm1.1Llli Speer6-ps1^{Tg(Alb-cre)21Mgn}

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:173666 )

• diethylnitrosamine (DEN)-challenged mice exhibit decreased survival compared with similarly treated wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality ( J:173666 )

• LPS-challenged mice exhibit decreased survival compared with similarly treated wild-type mice

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:173666 )

• diethylnitrosamine (DEN)-challenged mice exhibit decreased survival compared with similarly treated wild-type mice

immune system

increased susceptibility to bacterial infection induced morbidity/mortality ( J:173666 )

• LPS-challenged mice exhibit decreased survival compared with similarly treated wild-type mice

Genotype
MGI:3613531

cn2

• Allelic Composition: Ahr^tm3.1Bra/Ahr^tm3.1Bra; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Ahr^tm3.1Bra Speer6-ps1^{Tg(Alb-cre)21Mgn}

cardiovascular system

cardiovascular system phenotype ( J:104388 )

N • no defect in the closure of the ductus venosus is seen unlike in mice homozygous for Ahr^tm3Bra

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:104388 )

• exposure to 100 ug 2,3,7,8-tetrachlorodibenzo-p-dioxin failed to induce hepatomegaly, or Cyp1a2 expression, only weakly induced Cyp1a1 expression, partially induced Cyp1b1 expression, and resulted in significantly less liver damage compared to homozygous mice lacking the cre transgene

• however, exposure to 100 ug 2,3,7,8-tetrachlorodibenzo-p-dioxin did induce thymic involution similar to homozygous mice lacking the cre transgene

Genotype
MGI:6715351

cn3

• Allelic Composition: Dhcr24^{tm1c(EUCOMM)Wtsi}/Dhcr24^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Dhcr24^{tm1c(EUCOMM)Wtsi} Speer6-ps1^{Tg(Alb-cre)21Mgn}

homeostasis/metabolism

abnormal sterol level ( J:304449 )

• mice exhibit elevated liver, plasma, stool, and biliary levels of desmosterol

• mice exhibit slightly elevated lanosterol levels in the liver

• however, circulating levels of cholesterol are normal, sterol levels in the brains show no differences in cholesterol or desmosterol levels, and no changes in the levels of stool cholesterol are seen

decreased liver cholesterol level ( J:304449 )

♀ • hepatic cholesterol levels are slightly decreased in females

liver/biliary system

abnormal liver morphology ( J:304449 )

• liver shows elevated desmosterol level and slightly elevated lanosterol levels

• however, no differences are seen in liver cell morphology or hepatic lipid accumulation

decreased liver cholesterol level ( J:304449 )

♀ • hepatic cholesterol levels are slightly decreased in females

abnormal bile composition ( J:304449 )

• biliary desmosterol level is increased

• however, no differences in levels of biliary cholesterol, bile acids or biliary phospholipids are seen

digestive/alimentary system

abnormal feces composition ( J:304449 )

• stool desmosterol level is increased

Genotype
MGI:6690698

cn4

• Allelic Composition: Dhcr7^tm1.1Sbpa/Dhcr7^tm1.1Sbpa; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Dhcr7^tm1.1Sbpa Speer6-ps1^{Tg(Alb-cre)21Mgn}

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:303316 )

N • mice show no changes in parameters of glucose homeostasis, with unaltered glucose and insulin tolerance, unaltered plasma cholesterol levels, and no changes in hepatic triglyceride secretion rates

abnormal bile salt homeostasis ( J:303316 )

• desmosterol secretion into bile is decreased

• 7-DHC excretion into bile is increased

increased bile salt level ( J:303316 )

♂ • males show a small increase in levels of biliary bile acids

♂ • however, phospholipid levels do not differ in bile or plasma

abnormal sterol level ( J:303316 )

• mice exhibit an elevation of plasma levels of 7-dehydrocholesterol (DHC) and its isomer 8-DHC, and of lathosterol, and a decrease in plasma desmosterol levels

• females only show an increase in 7-dehydrodesmosterol (DHD), the immediate precursor to desmosterol

• males only show an increase in 24-dehydrolathosterol levels

• mice show altered sterol profiles in the liver, with elevated 7-DHC and 8-DHC levels

• males only show elevated levels of lathosterol and DHD in the liver

• however, no changes in levels of vitamin D3 or 25OH-vitamin D3 are seen and sterol profiles are unaltered in the brain

• the biliary sterol profile more closely mirrors the plasma sterol levels than the hepatic sterol levels

decreased liver cholesterol level ( J:303316 )

• females only show decreased levels of cholesterol and desmosterol in the liver

liver/biliary system

decreased liver cholesterol level ( J:303316 )

• females only show decreased levels of cholesterol and desmosterol in the liver

abnormal bile composition ( J:303316 )

• the cholesterol content of bile is similar to controls, but 7-DHC and 8-DHC in bile are elevated

• bile shows decreased desmosterol, increased 7-dehydrodesmosterol and lathosterol, but no difference in lanosterol

growth/size/body

growth/size/body region phenotype ( J:303316 )

N • body weight, percent body fat and lean mass (except for males at 10-14 weeks of age) are similar to wild-type

decreased lean body mass ( J:303316 )

♂ • males show a slightly lower lean body mass at 10-14 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Smith-Lemli-Opitz syndrome		DOID:14692	OMIM:270400	J:303316

Genotype
MGI:5662240

cn5

• Allelic Composition: Ggcx^tm1Sinos/Ggcx^tm1Sinos; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Ggcx^tm1Sinos Speer6-ps1^{Tg(Alb-cre)21Mgn}

mortality/aging

premature death ( J:212951 )

• mice are born alive and survive for at least several weeks but die of fatal bleeding as a result of bleeding diathesis, injury and pregnancy

• when kept separately without mating, female mice survive significantly longer than male mice

• male mice begin to die from day 27 after birth, and all males die within 80 days after birth

• female mice begin to die from day 39 after birth and 7 out of 11 (63.6%) survive longer than 100 days, unless they become pregnant

pregnancy-related premature death ( J:212951 )

♀ • pregnancy causes fatal vaginal and uterine bleeding

cardiovascular system

uterine hemorrhage ( J:212951 )

♀ • dissection of pregnant female mice just after death revealed uterine bleeding

vaginal hemorrhage ( J:212951 )

• dissection of pregnant female mice just after death revealed vaginal bleeding

subcutaneous hemorrhage ( J:212951 )

• at 9 weeks of age, massive subcutaneous bleeding is noted even before death

homeostasis/metabolism

impaired blood coagulation ( J:212951 )

• activities of vitamin K-dependent coagulation factors II and IX are significantly decreased relative to wild-type controls

increased bleeding time ( J:212951 )

• mice exhibit a bleeding diathesis and continue to bleed for >30 minutes after tail incision

• however, the platelet count is not significantly altered, suggesting that increased bleeding time is due to defective secondary coagulation

hematopoietic system

anemia ( J:212951 )

• mice appear to die of anemia secondary to bleeding

integument

subcutaneous hemorrhage ( J:212951 )

• at 9 weeks of age, massive subcutaneous bleeding is noted even before death

reproductive system

uterine hemorrhage ( J:212951 )

♀ • dissection of pregnant female mice just after death revealed uterine bleeding

vaginal hemorrhage ( J:212951 )

• dissection of pregnant female mice just after death revealed vaginal bleeding

Genotype
MGI:5662241

cn6

• Allelic Composition: Ggcx^tm1Sinos/Ggcx⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Ggcx^tm1Sinos Speer6-ps1^{Tg(Alb-cre)21Mgn}

mortality/aging

mortality/aging ( J:212951 )

N • none of the control heterozygotes died within the 100 days of the observation period

Genotype
MGI:5538628

cn7

• Allelic Composition: Hmgcl^tm2Gam/Hmgcl^tm2Gam; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Hmgcl^tm2Gam Speer6-ps1^{Tg(Alb-cre)21Mgn}

The leucine metabolite 2-ketoisocaproate induces liver steatosis in Hmgcl^tm2Gam/Hmgcl^tm2Gam Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

mortality/aging

premature death ( J:204294 )

• all mice die between 3 and 5 weeks following spontaneous episodes, or crises, of progressive lethargy, hypoglycemia and hyperammonia

• however, mice fed a low protein diet plus 10% glucose in drinking water exhibit diminished occurrence of crises

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:204294 )

N • mice exhibit normal peroxisome-related metabolites

increased circulating carnitine level ( J:204294 )

• elevated levels of leucine-related metabolites in stressed mice (following injection of KIC or during spontaneous crises)

• increased plasma acylcarnities in stressed mice

increased circulating ammonia level ( J:204294 )

• before death

• in mice treated with the leucine metabolite 2-ketoisocaproate (KIC)

• however, hyperammonemia is improved by carglumate treatment

hypoglycemia ( J:204294 )

• before death

• in mice treated with the leucine metabolite 2-ketoisocaproate (KIC)

abnormal gluconeogenesis ( J:204294 )

• reduced gluconeogenesis in hepatocytes

liver/biliary system

abnormal hepatocyte mitochondrial morphology ( J:204294 )

• dilated in hepatocytes

abnormal hepatocyte physiology ( J:204294 )

• undetectable ketogenesis from octanoate in hepatocytes

• reduced gluconeogenesis in hepatocytes

behavior/neurological

lethargy ( J:204294 )

• progressive 1 to 4 hours before death

cellular

abnormal hepatocyte mitochondrial morphology ( J:204294 )

• dilated in hepatocytes

Genotype
MGI:4439271

cn8

• Allelic Composition: Hs2st1^tm1.1Je/Hs2st1^tm1.1Je; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Hs2st1^tm1.1Je Speer6-ps1^{Tg(Alb-cre)21Mgn}

homeostasis/metabolism

abnormal lipid homeostasis ( J:158299 )

• mice exhibit slower plasma clearance of triglycerides and VLDL compared with wild-type mice

• however, plasma cholesterol levels are normal

increased circulating triglyceride level ( J:158299 )

• 2-fold

liver/biliary system

abnormal hepatocyte physiology ( J:158299 )

• hepatocytes exhibit decreased VLDL binding, uptake, and degradation compared with wild-type cells

Genotype
MGI:5897809

cn9

• Allelic Composition: Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz; Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Mob1b^{Gt(CC0690)Wtsi} Mob1a^tm1.1Asuz Speer6-ps1^{Tg(Alb-cre)21Mgn}

mortality/aging

premature death ( J:228499 )

• all mice are dead by 60 weeks

postnatal lethality, incomplete penetrance ( J:228499 )

• the first mice die at P14 and more than half of mice die by P21

liver/biliary system

liver/biliary system phenotype ( J:228499 )

N • mice exhibit normal liver structure at P0

increased hepatocyte proliferation ( J:228499 )

• 3 times in controls

abnormal cholangiocyte morphology ( J:228499 )

• at P7, mice exhibit increased immature cholangiocyte-like and oval cells that becomes massive at P10 especially in periductal and intraductal locations

• mild hepatocholangiocellular hyperplasia at P21

enlarged liver ( J:228499 )

• massive

increased hepatocyte number ( J:228499 )

• 5 times greater than in control mice at P14

liver fibrosis ( J:228499 )

increased hepatobiliary system tumor incidence ( J:228499 )

• combined hepatocellular and cholangiocarcinomas, increased hepatocellular carcinoma, liver adenoma incidence or cholangiocarcinoma in 8 of 10 mice surviving beyond P21 by age 15 weeks

• combined hepatocellular and cholangiocarcinomas in 13 of 22 mice at week 60

• with lung metastasis after 40 weeks of age

increased cholangiocarcinoma incidence ( J:228499 )

• intrahepatic cholangiocellular carcinoma in 8 of 10 mice surviving beyond P21 by age 15 weeks

• in 2 of 22 mice at week 60

increased hepatocellular carcinoma incidence ( J:228499 )

• in mice surviving beyond P21 by age 15 weeks

• in 4 of 22 mice at week 60

increased liver adenoma incidence ( J:228499 )

• in mice surviving beyond P21 by age 15 weeks

abnormal bile duct physiology ( J:228499 )

• cholangiocytes proliferation is increased 4 times compared with controls

• however, there is no increase in apoptosis

jaundice ( J:228499 )

neoplasm

increased hepatobiliary system tumor incidence ( J:228499 )

• combined hepatocellular and cholangiocarcinomas, increased hepatocellular carcinoma, liver adenoma incidence or cholangiocarcinoma in 8 of 10 mice surviving beyond P21 by age 15 weeks

• combined hepatocellular and cholangiocarcinomas in 13 of 22 mice at week 60

• with lung metastasis after 40 weeks of age

increased cholangiocarcinoma incidence ( J:228499 )

• intrahepatic cholangiocellular carcinoma in 8 of 10 mice surviving beyond P21 by age 15 weeks

• in 2 of 22 mice at week 60

increased hepatocellular carcinoma incidence ( J:228499 )

• in mice surviving beyond P21 by age 15 weeks

• in 4 of 22 mice at week 60

increased liver adenoma incidence ( J:228499 )

• in mice surviving beyond P21 by age 15 weeks

homeostasis/metabolism

increased circulating bilirubin level ( J:228499 )

integument

abdomen swellings ( J:228499 )

• due to enlarged liver

cellular

increased hepatocyte proliferation ( J:228499 )

• 3 times in controls

endocrine/exocrine glands

abnormal cholangiocyte morphology ( J:228499 )

• at P7, mice exhibit increased immature cholangiocyte-like and oval cells that becomes massive at P10 especially in periductal and intraductal locations

• mild hepatocholangiocellular hyperplasia at P21

increased cholangiocarcinoma incidence ( J:228499 )

• intrahepatic cholangiocellular carcinoma in 8 of 10 mice surviving beyond P21 by age 15 weeks

• in 2 of 22 mice at week 60

growth/size/body

enlarged liver ( J:228499 )

• massive

Genotype
MGI:3697677

cn10

• Allelic Composition: Scarb1^tm1Thh/Scarb1^tm1Thh; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Scarb1^tm1Thh Speer6-ps1^{Tg(Alb-cre)21Mgn}

homeostasis/metabolism

increased circulating cholesterol level ( J:114663 )

• elevation in plasma total cholesterol that is associated with more than 3-fold increase in free cholesterol

• high increase in plasma free cholesterol/plasma total cholesterol ratio

• develop severe hypercholesterolemia on an atherogenic diet due to an accumulation of free cholesterol-rich, VLDL-sized particles

• hepatic content of free and esterified cholesterol is normal

increased circulating HDL cholesterol level ( J:114663 )

• marked elevation of HDL cholesterol with abnormally large HDL particles

increased circulating interleukin-6 level ( J:114663 )

• on an atherogenic diet, IL-6 plasma levels are 6.6-fold greater than in wild-type

cardiovascular system

increased susceptibility to atherosclerosis ( J:114663 )

• atherosclerosis is enhanced 32-fold compared to controls, when fed an atherogenic (high-fat, high-cholesterol, and cholic acid-containing) diet

immune system

increased circulating interleukin-6 level ( J:114663 )

• on an atherogenic diet, IL-6 plasma levels are 6.6-fold greater than in wild-type

Genotype
MGI:4867849

cn11

• Allelic Composition: Ahr^b-1/Ahr^b-1; Aip^tm2.1Bra/Aip^tm2.1Bra; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Speer6-ps1^{Tg(Alb-cre)21Mgn} Aip^tm2.1Bra

Ahr^b-1/Ahr^b-1 Aip^tm2.1Bra/Aip^tm2.1Bra Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice are resistant to dioxin-induced hepatic damage

homeostasis/metabolism

abnormal circulating alanine transaminase level ( J:166864 )

• doxin-treated mice do not exhibit an increase in serum alanine transaminase unlike similarly treated Aip^tm2.1Bra homozygotes

decreased physiological sensitivity to xenobiotic ( J:166864 )

• doxin-treated mice do not exhibit an increase in serum alanine transferase and are resistant to induced hepatic damage unlike similarly treated Aip^tm2.1Bra homozygotes

• however, doxin-treated mice exhibit increased liver and thymus weight similar to wild-type mice

cardiovascular system

patent ductus venosus ( J:166864 )

• in 1 of 8 mice

growth/size/body

decreased body size ( J:166864 )

• at 8 weeks

cellular

patent ductus venosus ( J:166864 )

• in 1 of 8 mice

Genotype
MGI:5317915

cn12

• Allelic Composition: Naa40^tm1Qwzh/Naa40^tm1Qwzh; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Speer6-ps1^{Tg(Alb-cre)21Mgn} Naa40^tm1Qwzh

homeostasis/metabolism

increased circulating glucose level ( J:183119 )

• in fasting mice

increased energy expenditure ( J:183119 )

• at 22 weeks, but not 9 weeks, in male mice when normalized to body weight

increased oxygen consumption ( J:183119 )

• at 22 weeks, but not 9 weeks, in male mice when normalized to body weight

decreased respiratory quotient ( J:183119 )

• during the dark cycle in male mice at 22 weeks

improved glucose tolerance ( J:183119 )

• slight in male mice, but not female mice

abnormal lipid homeostasis ( J:183119 )

• hepatocytes exhibit decreased relative lipid synthesis compared with control cells

increased fatty acid oxidation ( J:183119 )

• fatty acid oxidation in the liver of male mice is increased compared to in control mice

decreased circulating LDL cholesterol level ( J:183119 )

• in fasting mice

decreased circulating VLDL triglyceride level ( J:183119 )

• at 9 weeks, but not 31 weeks, in male mice

decreased liver free fatty acids level ( J:183119 )

• at 31 weeks in male mice

decreased liver triglyceride level ( J:183119 )

• at 31 weeks in male mice

liver/biliary system

decreased liver free fatty acids level ( J:183119 )

• at 31 weeks in male mice

decreased liver triglyceride level ( J:183119 )

• at 31 weeks in male mice

decreased susceptibility to age-related hepatic steatosis ( J:183119 )

• induced by age or palmitic acid

• however, mice exhibit normal susceptibility to high fat diet-induced steatosis

adipose tissue

decreased total body fat amount ( J:183119 )

• at 6, 9 and 20 weeks

decreased percent body fat/body weight ( J:183119 )

• at 6, 9 and 20 weeks

growth/size/body

increased lean body mass ( J:183119 )

• lean mass and content at 20 weeks in male mice, but not female mice

increased body weight ( J:183119 )

• slight in male mice, but not female mice

behavior/neurological

abnormal eating behavior ( J:183119 )

• slight in female and male mice fed standard chow

• in male mice fed a high fat diet

cellular

increased fatty acid oxidation ( J:183119 )

• fatty acid oxidation in the liver of male mice is increased compared to in control mice

Genotype
MGI:6361078

cn13

• Allelic Composition: Rubcnl^em1Qsun/Rubcnl^em1Qsun; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Speer6-ps1^{Tg(Alb-cre)21Mgn} Rubcnl^em1Qsun

liver/biliary system

increased liver weight ( J:272052 )

• liver weight to body weight ratio is significantly increased at 12 weeks of age

• however, body weight is normal

increased liver glycogen level ( J:272052 )

• hepatic glycogen levels are significantly increased at 8 weeks of age

increased liver triglyceride level ( J:272052 )

• hepatic triglyceride levels are significantly increased at 12 weeks of age

hepatic steatosis ( J:272052 )

• Oil red O staining revealed lipid accumulation in liver tissues at 8 weeks of age

liver fibrosis ( J:272052 )

• collagen deposition is significantly increased at 8 weeks of age, suggesting liver fibrosis

• however, no severe hepatomegaly or tumorigenesis are observed over a period of 4 months after birth

abnormal liver physiology ( J:272052 )

• after 24 h of fasting, liver tissue ketone body levels are significantly lower than those in wild-type controls

• however, liver tissue ketone body levels are normal under fed conditions

homeostasis/metabolism

impaired autophagy ( J:272052 )

• protein levels of the autophagy markers p62 and LC3 are increased in the liver at 8 weeks of age, indicating impaired autophagosome maturation

• TEM analysis revealed a significantly increased number of autophagosomes surrounding lipid droplets in hepatocytes at 12 weeks of age

decreased circulating ketone body level ( J:272052 )

• after 24 h of fasting, total serum ketone body levels are significantly lower than those in wild-type controls

• however, total serum ketone body levels are normal under fed conditions

increased liver glycogen level ( J:272052 )

• hepatic glycogen levels are significantly increased at 8 weeks of age

increased liver triglyceride level ( J:272052 )

• hepatic triglyceride levels are significantly increased at 12 weeks of age

cellular

impaired autophagy ( J:272052 )

• protein levels of the autophagy markers p62 and LC3 are increased in the liver at 8 weeks of age, indicating impaired autophagosome maturation

• TEM analysis revealed a significantly increased number of autophagosomes surrounding lipid droplets in hepatocytes at 12 weeks of age

growth/size/body

increased liver weight ( J:272052 )

• liver weight to body weight ratio is significantly increased at 12 weeks of age

• however, body weight is normal

Genotype
MGI:3773310

cn14

• Allelic Composition: Scd1^tm2Ntam/Scd1^tm2Ntam; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Speer6-ps1^{Tg(Alb-cre)21Mgn} Scd1^tm2Ntam

growth/size/body

decreased susceptibility to diet-induced obesity ( J:130441 )

• resistant to high carbohydrate and high-sucrose very low-fat, but not high fat, diet-induced obesity

adipose tissue

decreased white adipose tissue amount ( J:130441 )

• reduced by 51% in mice on a high-sucrose very low-fat diet compared to diet matched controls

abnormal fat pad morphology ( J:130441 )

• on a high carbohydrate diet weights of the gonadal, retroperitioneal, and inguinal fat pads are reduced by about 49% - 59% compared to controls lacking the cre transgene

decreased gonadal fat pad weight ( J:130441 )

• reduced weight on a high carbohydrate diet compared to diet matched controls

decreased inguinal fat pad weight ( J:130441 )

• reduced weight on a high carbohydrate diet compared to diet matched controls

decreased retroperitoneal fat pad weight ( J:130441 )

• reduced weight on a high carbohydrate diet compared to diet matched controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:130441 )

N • unlike global null mice, no difference is seen in plasma glucose and insulin levels, glucose clearance or insulin sensitivity between liver knockout mice and controls on a high carbohydrate diet

decreased susceptibility to diet-induced obesity ( J:130441 )

• resistant to high carbohydrate and high-sucrose very low-fat, but not high fat, diet-induced obesity

decreased circulating glucose level ( J:130441 )

• reduced in mice on a high-sucrose very low-fat diet compared to diet matched controls

• but not in mice on high carbohydrate, high fat, or chow diet

• supplementing the high-sucrose very low-fat diet with oleate prevents the decrease in plasma glucose levels

abnormal gluconeogenesis ( J:130441 )

• impaired production of glucose from pyruvate in mice fed a high-sucrose very low-fat diet

decreased liver glycogen level ( J:130441 )

• reduced glycogen levels in the liver in mice on a high-sucrose very low-fat diet compared to diet matched controls

• supplementing the diet with oleate prevents the decrease in hepatic glycogen levels

abnormal lipid homeostasis ( J:130441 )

• 85% decrease in hepatic lipogenesis in mice on a high carbohydrate diet

• however, cholesterol synthesis is unaffected

increased circulating cholesterol level ( J:130441 )

• develops in mice on a high-sucrose very low-fat diet, probably due to increases in HDL and LDL cholesterol

decreased circulating triglyceride level ( J:130441 )

• in mice on a high carbohydrate diet compared to diet-matched controls

• however, levels are similar to controls in mice on a chow or high fat diet

decreased circulating VLDL triglyceride level ( J:130441 )

• significant reduction in mice on a high carbohydrate or a high-sucrose very low-fat diet compared to diet-matched controls

decreased liver triglyceride level ( J:130441 )

• on a high carbohydrate or diet high-sucrose very low-fat diet, liver triglyceride levels are reduced by 69% or 49%, respectively, compared to controls

• fasted mice refed a fat free high carbohydrate diet have lower liver levels of SCD1 products including palmitoleate and oleate

• supplementing the diet with triolein reduces the decrease in liver triglyceride levels

liver/biliary system

decreased liver glycogen level ( J:130441 )

• reduced glycogen levels in the liver in mice on a high-sucrose very low-fat diet compared to diet matched controls

• supplementing the diet with oleate prevents the decrease in hepatic glycogen levels

decreased liver triglyceride level ( J:130441 )

• on a high carbohydrate or diet high-sucrose very low-fat diet, liver triglyceride levels are reduced by 69% or 49%, respectively, compared to controls

• fasted mice refed a fat free high carbohydrate diet have lower liver levels of SCD1 products including palmitoleate and oleate

• supplementing the diet with triolein reduces the decrease in liver triglyceride levels

decreased susceptibility to diet-induced hepatic steatosis ( J:130441 )

• resistant to high carbohydrate and high-sucrose very low-fat, but not high fat, diet-induced fatty liver development

abnormal liver physiology ( J:130441 )

• block in carbohydrate-induce hepatic lipogenesis

• a high-sucrose very low-fat diet fails to increase the rate of triglyceride secretion, unlike in controls

behavior/neurological

behavior/neurological phenotype ( J:130441 )

N • unlike global null mice, no difference in food intake is seen in mice on a chow diet

Genotype
MGI:7384742

cn15

• Allelic Composition: Ssu72^tm1Cwl/Ssu72^tm1Cwl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Ssu72^tm1Cwl Speer6-ps1^{Tg(Alb-cre)21Mgn}

liver/biliary system

liver inflammation ( J:309624 )

• livers show inflammatory cell infiltration

• expansion of liver macrophages

• elevation of intrahepatic IL-1beta, IL-6, and TNF-alpha levels

abnormal liver morphology ( J:309624 )

• 12-month old mice show signs of liver disease, including fatty change, necrosis, inflammatory cell infiltration, and increased liver injury with impaired liver damage response

increased liver weight ( J:309624 )

• ratio of liver weight to body weight is slightly increased in 5-week-old mice

abnormal liver development ( J:309624 )

• hepatocytes show aberrant chromosome polyploidy during postnatal liver development

abnormal hepatocyte morphology ( J:309624 )

• primary hepatocytes show higher proportions of octoploid hepatocytes but almost no diploid hepatocytes after weaning compared to wild-type hepatocytes which show increased tetraploid and octoploid and lower diploid after weaning, indicating an increase of the hepatic polyploidy population

• the proportion of octoploid hepatocytes gradually increase with age to reach almost 60% at 10 weeks whereas fewer than 20% of octoploid hepatocytes are seen in wild-type mice at the same age

• however, hepatocytes are composed of predominately diploid, with some tetraploid, before weaning as in wild-type hepatocytes and primary mouse embryonic fibroblasts exhibit normal diploidy

• livers show a decrease in the proportion of binucleated hepatocytes starting at 5 weeks of age

• livers show an increase in the size of mononuclear hepatocytes at 10 weeks of age

• livers show cytomegalic hepatocytes and cytoplasmic vacuolization

increased hepatocyte karyomegaly ( J:309624 )

• livers show an increase in nuclear diameters of mononuclear hepatocytes at 10 weeks of age

abnormal Ito cell morphology ( J:309624 )

• increase in the appearance and expansion of activated hepatic stellate cells

hepatic necrosis ( J:309624 )

hepatic steatosis ( J:309624 )

• livers show extensive steatosis, with increased lipid deposition in the hepatocytes and hepatocyte ballooning, characteristic of nonalcoholic steatohepatitis

liver fibrosis ( J:309624 )

• fibrillar collagen initially seen around the portal veins gradually increases such that many livers are fibrotic at 5 and 10 weeks of age

abnormal hepatocyte physiology ( J:309624 )

• hepatocyte cell cycle is arrested at G2 phase and/or delayed in the G2 to mitosis transition, however aberrant polyploid hepatocytes are able to reenter the cell cycle despite the G2/M arrest

increased hepatocyte apoptosis ( J:309624 )

• increase in hepatocyte apoptosis, particularly at 5 weeks

increased hepatocyte proliferation ( J:309624 )

• 5-week-old mice show an increase in hepatocyte proliferation

cellular

increased hepatocyte karyomegaly ( J:309624 )

• livers show an increase in nuclear diameters of mononuclear hepatocytes at 10 weeks of age

increased hepatocyte apoptosis ( J:309624 )

• increase in hepatocyte apoptosis, particularly at 5 weeks

increased hepatocyte proliferation ( J:309624 )

• 5-week-old mice show an increase in hepatocyte proliferation

growth/size/body

increased liver weight ( J:309624 )

• ratio of liver weight to body weight is slightly increased in 5-week-old mice

homeostasis/metabolism

increased circulating alanine transaminase level ( J:309624 )

• alanine aminotransferase (ALT) levels are highly elevated after weaning (5, 10, 20, and 52 weeks of age) but not at 3 weeks of age

increased circulating aspartate transaminase level ( J:309624 )

• aspartate aminotransferase (AST) levels are highly elevated after weaning but not at 3 weeks of age

increased physiological sensitivity to xenobiotic ( J:309624 )

• mice show increased susceptibility to carbon tetracholoride-induced liver damage, showing more severe liver necrosis and fibrosis and higher ALT, AST, and apoptosis levels, and elevation of intrahepatic fibrogenic cytokines such as IL-6 and TNF-alpha

immune system

liver inflammation ( J:309624 )

• livers show inflammatory cell infiltration

• expansion of liver macrophages

• elevation of intrahepatic IL-1beta, IL-6, and TNF-alpha levels

neoplasm

neoplasm ( J:309624 )

N • hepatocellular carcinoma is not seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
liver disease		DOID:409		J:309624

Genotype
MGI:3629066

cn16

• Allelic Composition: Abcb7^tm1Mdf/Y; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: either: B6.Cg-Speer6-ps1^{Tg(Alb-cre)21Mgn} Abcb7^tm1Mdf or (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * DBA)

cellular

increased polyploid hepatocyte number ( J:106838 )

• mild hepatocellular multinucleation

abnormal hepatocyte mitochondrial morphology ( J:106838 )

• pale, swollen mitochondria

liver/biliary system

abnormal liver morphology ( J:106838 )

♂ • mild hepatic architectural disarray and hepatocellular multinucleation are seen

abnormal hepatocyte morphology ( J:106838 )

♂ • many cytosolic lipid droplets and pale swollen mitochondria are seen suggesting metabolic or mitochondrial damage

♂ • multinucleated hepatocytes are seen

increased polyploid hepatocyte number ( J:106838 )

• mild hepatocellular multinucleation

abnormal hepatocyte mitochondrial morphology ( J:106838 )

• pale, swollen mitochondria

homeostasis/metabolism

abnormal circulating enzyme level ( J:106838 )

♂ • 2-fold increase in serum levels of liver-derived transaminases indicative of liver damage

hemosiderosis ( J:106838 )

♂ • 76% increase in total liver iron; however, serum iron and total iron binding capacity are similar to controls and no signs of mitochondrial iron overload are detected

♂ • a small subset of hepatocytes particularly cells adjacent to a portal triad or central vein, contain abundant, coarsely granular cytosolic iron deposits

abnormal enzyme/coenzyme activity ( J:106838 )

♂ • 50% reduction in hepatic activity of xanthine oxidase; however no change in expression is detected

♂ • about a 20% decrease in hepatic mitochondrial activity of succinate dehydrogenase when normalized to cytochrome C oxidase activity

♂ • about a 90% and 60% decrease in cytosolic aconitate hydratase 1 (Aco1) activity and protein, respectivly, are seen in the liver

Genotype
MGI:5316849

cn17

• Allelic Composition: Cav1^tm1Pesch/Cav1^tm1Pesch; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: FVB.Cg-Cav1^tm1Pesch Speer6-ps1^{Tg(Alb-cre)21Mgn}

homeostasis/metabolism

decreased circulating glucose level ( J:182288 )

• small but significant reduction in fasted glucose levels

decreased circulating glycerol level ( J:182288 )

• following 3-mercaptopicolinic acid treatment

liver/biliary system

liver/biliary system phenotype ( J:182288 )

N • fasting induced steatosis and glycerol induced glucose production are similar to wild-type mice

Genotype
MGI:5824005

cn18

• Allelic Composition: Stk3^tm1Jav/Stk3^tm1Jav; Stk4^{Gt(AJ0315)Wtsi}/Stk4^{Gt(AJ0315)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

increased hepatocellular carcinoma incidence ( J:238319 )

• mice develop multiple spontaneous hepatocellular carcinomas

neoplasm

increased hepatocellular carcinoma incidence ( J:238319 )

• mice develop multiple spontaneous hepatocellular carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:238319

Genotype
MGI:3621473

cn19

• Allelic Composition: Arnt^tm1Bra/Arnt^tm1Bra; Vhl^tm1Jae/Vhl^tm1Jae; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * BALB/c * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:97652 )

N • livers appear histologically normal at 4 - 6 weeks of age

Genotype
MGI:3621471

cn20

• Allelic Composition: Hif1a^tm3Rsjo/Hif1a^tm3Rsjo; Vhl^tm1Jae/Vhl^tm1Jae; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * BALB/c * C57BL/6 * DBA

liver/biliary system

hepatic steatosis ( J:97652 )

• severe steatosis

cardiovascular system

increased vascular endothelial cell number ( J:97652 )

• proliferation of endothelial cells in hepatic blood vessels

abnormal vasodilation ( J:97652 )

• hepatic vascular angiectasia

muscle

abnormal vasodilation ( J:97652 )

• hepatic vascular angiectasia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:97652

Genotype
MGI:4411991

cn21

• Allelic Composition: Stk3^tm1Jav/Stk3^tm1Jav; Stk4^{Gt(AJ0315)Wtsi}/Stk4^{Gt(AJ0315)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6

liver/biliary system

liver hyperplasia ( J:153945 )

• develop massively overgrown livers by 3 months of age (4 out of 4)

increased hepatocellular carcinoma incidence ( J:153945 )

• develop hepatocellular carcinomas (HHCs) by 3 months of age (4 out of 4)

neoplasm

increased hepatocellular carcinoma incidence ( J:153945 )

• develop hepatocellular carcinomas (HHCs) by 3 months of age (4 out of 4)

growth/size/body

liver hyperplasia ( J:153945 )

• develop massively overgrown livers by 3 months of age (4 out of 4)

Genotype
MGI:6711445

cn22

• Allelic Composition: Wwc1^tm1Arsc/Wwc1^tm1Arsc; Wwc2^tm1.1Arte/Wwc2^tm1.1Arte; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * DBA

liver/biliary system

abnormal liver morphology ( J:305034 )

• 3-month-old mice exhibit liver overgrowth

• however, liver does not show alterations in canalicular morphology, hepatocyte ultrastructure, or hepatic plate thickness, indicating normal hepatocyte polarity

increased liver weight ( J:305034 )

• 3-month-old mice exhibit increased liver weight relative to total body weight, which is increased in 6-month-old mice and is about 5-fold higher than in controls at 12 months of age

abnormal portal triad morphology ( J:305034 )

• liver shows massive enrichment of small cells at portal triads

• liver shows malformation of the portal triads with an increase of ductal structures

• however, the arrangement of hepatic cells close to the central vein appears normal

increased liver tumor incidence ( J:305034 )

• 12-month-old mice exhibit numerous liver tumors that have characteristics of both hepatocellular carcinoma and cholangiocarcinoma, possibly representing an intermediate tumor phenotype

• tumors show cells with enlarged, atypical nuclei and irregular arrangements of hepatocytes, and the border between each tumor and normal liver tissue is made up of a collagen-rich capsule

liver fibrosis ( J:305034 )

• liver shows the presence of fibrotic areas close to portal triads and in the periportal zones

abnormal liver physiology ( J:305034 )

• 6-month-old livers show enhanced proliferation of immature biliary epithelial cell-like progenitor cells

liver inflammation ( J:305034 )

• livers show an enrichment of activated myofibroblasts and infiltration with inflammatory macrophages

neoplasm

increased liver tumor incidence ( J:305034 )

• 12-month-old mice exhibit numerous liver tumors that have characteristics of both hepatocellular carcinoma and cholangiocarcinoma, possibly representing an intermediate tumor phenotype

• tumors show cells with enlarged, atypical nuclei and irregular arrangements of hepatocytes, and the border between each tumor and normal liver tissue is made up of a collagen-rich capsule

growth/size/body

increased liver weight ( J:305034 )

• 3-month-old mice exhibit increased liver weight relative to total body weight, which is increased in 6-month-old mice and is about 5-fold higher than in controls at 12 months of age

immune system

liver inflammation ( J:305034 )

• livers show an enrichment of activated myofibroblasts and infiltration with inflammatory macrophages

Genotype
MGI:5762654

cn23

• Allelic Composition: Gfer^tm1.1Crg/Gfer^tm1.1Crg; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA

liver/biliary system

abnormal liver morphology ( J:227242 )

• progressively coarsened and granular by 8 weeks

• after 6 months, mice develop nodular foci of high-grade dysplasia in the liver

abnormal hepatocyte mitochondrial morphology ( J:227242 )

• swollen, abnormally shaped and with increased spacing or loss of cristae in hepatocyte mitochondria at 2 weeks of age; persistent to a lesser magnitude at 8 weeks

increased liver weight ( J:227242 )

• higher liver to body weight ratio at 4 to 6 weeks

decreased liver cholesterol level ( J:227242 )

• at 8 weeks of age

increased liver cholesterol level ( J:227242 )

• modestly at 2 weeks of age

• however, levels are normal at 4 weeks of age

increased liver triglyceride level ( J:227242 )

• at 2 and 4 weeks of age

• however, levels are normal at 8 weeks of age

hepatic necrosis ( J:227242 )

• at 8 weeks of age

focal hepatic necrosis ( J:227242 )

• focal hepatocyte necrosis at 4 weeks of age

hepatic steatosis ( J:227242 )

• macro- and micro vesicular steatosis with hepatocyte swelling and minimal inflammation at 2 weeks of age

• reduced at 4 weeks of age

macrovesicular hepatic steatosis ( J:227242 )

microvesicular hepatic steatosis ( J:227242 )

increased hepatocellular carcinoma incidence ( J:227242 )

• at 1 year, most mice develop hepatocellular carcinomas with tumor cells that are pleomorphic and often steatotic with frequent mitotic figures and variably anaplastic nuclei

liver fibrosis ( J:227242 )

• pericellular fibrosis at 2 weeks of age

• periportal fibrosis at 4 weeks of age

• bridging fibrosis at 8 weeks of age

pale liver ( J:227242 )

• milky white by 2 weeks of age

• however, livers regain normal color by 4 weeks

abnormal liver physiology ( J:227242 )

• prominent bile ductular proliferation at 4 weeks of age

• ductular proliferation at 8 weeks of age

• atypical ductular proliferation at 2 and 4 weeks of age

• cellular proliferation occurs in oval/biliary cells and parenchyma at 4 and 8 weeks of age

increased hepatocyte apoptosis ( J:227242 )

• at 2 weeks of age but decreasing progressively at 4 and 8 weeks of age

increased hepatocyte proliferation ( J:227242 )

• at 4 and 8 weeks

liver inflammation ( J:227242 )

• scattered lobular mixed inflammation with focal hepatocyte necrosis and prominent bile ductular proliferation at 4 weeks of age

• increasing portal/perioral and lobular mixed inflammation

abnormal oval cell physiology ( J:227242 )

• increased proliferation at 4 and 8 weeks of age

homeostasis/metabolism

increased circulating alanine transaminase level ( J:227242 )

• at 4 and 8 weeks of age

decreased liver cholesterol level ( J:227242 )

• at 8 weeks of age

increased liver cholesterol level ( J:227242 )

• modestly at 2 weeks of age

• however, levels are normal at 4 weeks of age

increased liver triglyceride level ( J:227242 )

• at 2 and 4 weeks of age

• however, levels are normal at 8 weeks of age

growth/size/body

decreased body weight ( J:227242 )

• at 4 and 6 weeks

• however, body weight is normal at 1, 2 and 8 weeks

increased liver weight ( J:227242 )

• higher liver to body weight ratio at 4 to 6 weeks

cellular

abnormal endoplasmic reticulum morphology ( J:227242 )

• dilated in hepatocytes with robust lipid deposition at 2 weeks of age; persistent to a lesser magnitude at 8 weeks

abnormal hepatocyte mitochondrial morphology ( J:227242 )

• swollen, abnormally shaped and with increased spacing or loss of cristae in hepatocyte mitochondria at 2 weeks of age; persistent to a lesser magnitude at 8 weeks

abnormal mitochondrial crista morphology ( J:227242 )

• increased spacing or loss of cristae in hepatocyte mitochondria at 2 weeks of age

abnormal mitochondrial shape ( J:227242 )

• in hepatocyte mitochondria at 2 weeks of age

decreased mitochondrial number ( J:227242 )

• in hepatocyte at 2 weeks of age

dilated mitochondrion ( J:227242 )

• in hepatocyte mitochondria at 2 weeks of age

increased hepatocyte apoptosis ( J:227242 )

• at 2 weeks of age but decreasing progressively at 4 and 8 weeks of age

increased hepatocyte proliferation ( J:227242 )

• at 4 and 8 weeks

abnormal cellular respiration ( J:227242 )

• in hepatocyte mitochondria at 2 weeks of age

• however, respiration activity has recovered by 4 and 8 weeks of age

neoplasm

increased hepatocellular carcinoma incidence ( J:227242 )

• at 1 year, most mice develop hepatocellular carcinomas with tumor cells that are pleomorphic and often steatotic with frequent mitotic figures and variably anaplastic nuclei

immune system

liver inflammation ( J:227242 )

• scattered lobular mixed inflammation with focal hepatocyte necrosis and prominent bile ductular proliferation at 4 weeks of age

• increasing portal/perioral and lobular mixed inflammation

Genotype
MGI:6358148

cn24

• Allelic Composition: Mia2^tm1Zhxu/Mia2^tm1Zhxu; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA

growth/size/body

decreased body size ( J:268333 )

• mice are smaller 1 month after birth

enlarged liver ( J:268333 )

• livers are enlarged in 2-week old mice

homeostasis/metabolism

decreased circulating cholesterol level ( J:268333 )

• total plasma cholesterol levels are reduced in P35 and P90 mice fed normally or under fasting conditions

decreased circulating triglyceride level ( J:268333 )

• total plasma triglyceride levels are reduced in P35 and P90 mice fed normally or under fasting conditions

• however, P35 and P90 mice exhibit normal albumin and glucose levels under fasting conditions

increased liver cholesterol level ( J:268333 )

• total cholesterol levels in the liver are increased in P35 mice fed a normal chow diet or when fasted for 16 hours

• however liver total cholesterol levels are similar to controls in P90 fasted mice

increased liver triglyceride level ( J:268333 )

• liver triglyceride levels are increased in in P35 mice fed a normal chow diet or when fasted for 16 hours and in P90 fasted mice

liver/biliary system

abnormal liver morphology ( J:268333 )

• 30% of livers develop nodular morphology with lipid storage disease-like structures in 1 year old mice

enlarged liver ( J:268333 )

• livers are enlarged in 2-week old mice

increased liver cholesterol level ( J:268333 )

• total cholesterol levels in the liver are increased in P35 mice fed a normal chow diet or when fasted for 16 hours

• however liver total cholesterol levels are similar to controls in P90 fasted mice

increased liver triglyceride level ( J:268333 )

• liver triglyceride levels are increased in in P35 mice fed a normal chow diet or when fasted for 16 hours and in P90 fasted mice

abnormal hepatocyte morphology ( J:268333 )

• size and number of lipid droplets are increased in hepatocytes

• hepatocytes exhibit distended endoplasmic reticulum and particles with density similar to lipid droplets are seen in the lumen

• small particles with density similar to lipid droplets are not seen within the membrane-bound secretory vesicles of the Golgi apparatus as in wild-type hepatocytes

hepatic steatosis ( J:268333 )

• fatty liver is seen as early as P1 and through adulthood

• size and number of lipid droplets are increased in hepatocytes

pale liver ( J:268333 )

• livers are pale in 2-week old mice

abnormal liver physiology ( J:268333 )

• quantitative lipidomic and proteomic analyses indicate impaired secretion of different types of lipids and proteins, including VLDL, from the liver

Genotype
MGI:3694896

cn25

• Allelic Composition: Ppargc1a^tm2Brsp/Ppargc1a^tm2Brsp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA

cellular

abnormal cell physiology ( J:115197 )

• fasting-mediated induction of aminolevulinic acid synthase is decreased in mutants compared to wild-type

homeostasis/metabolism

abnormal blood homeostasis ( J:115197 )

• injection of lead chloride into fasted mice does not alter serum gamma-aminolevulinic acid (ALA) or porphobilinogen (PBG) in contrast to increased levels observed in wild-type

Genotype
MGI:4459910

cn26

• Allelic Composition: Hif1an^tm1.1Rsjo/Hif1an^tm1.1Rsjo; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA

normal phenotype

no abnormal phenotype detected ( J:160941 )

Genotype
MGI:5318109

cn27

• Allelic Composition: Cdk1^tm2.1Kald/Cdk1^tm2.1Kald; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA * SJL

Livers of Cdk1^tm2.1Kald/Cdk1^tm2.1Kald Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice conatin fewer hepatocytes

liver/biliary system

decreased hepatocyte proliferation ( J:182141 )

• following partial hepatectomy, hepatocytes fail to enter cell division unlike control cells

• however, DNA replication is normal

abnormal hepatocyte morphology ( J:182141 )

• in untreated mice and following partial hepatectomy, hepatocytes exhibit increased nuclei diameter and decreased cell density compared with control cells

decreased hepatocyte number ( J:182141 )

• in untreated mice and following partial hepatectomy

cellular

polyploidy ( J:182141 )

• in hepatocytes following partial hepatectomy

abnormal mitosis ( J:182141 )

• following partial hepatectomy, hepatocytes fail to enter mitosis unlike control cells

decreased hepatocyte proliferation ( J:182141 )

• following partial hepatectomy, hepatocytes fail to enter cell division unlike control cells

• however, DNA replication is normal

neoplasm

decreased incidence of induced tumors ( J:182141 )

• following tail-vein injection of activated Ras, mice fail to develop liver tumors unlike control mice

homeostasis/metabolism

abnormal response to injury ( J:182141 )

• following partial hepatectomy, hepatocytes fail to enter cell division unlike control cells

• however, liver regeneration is achieved through cell growth

Genotype
MGI:6106901

cn28

• Allelic Composition: Nr1h3^tm1Djm/Nr1h3^tm1Djm; Nus1^tm1.1Qrm/Nus1^tm1.1Qrm; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA * SJL

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:243753 )

♀N • when fed Western diet

♀N • circulating triglyceride level

♀N • liver triglyceride level

♀N • circulating free fatty acid level

♀N • liver free fatty acid level

♀N • circulating cholesterol level both total and free

increased liver cholesterol level ( J:243753 )

♀ • both total and free when fed Western diet

liver/biliary system

increased liver cholesterol level ( J:243753 )

♀ • both total and free when fed Western diet

Genotype
MGI:6106900

cn29

• Allelic Composition: Nus1^tm1.1Qrm/Nus1^tm1.1Qrm; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129 * C57BL/6 * DBA * SJL

homeostasis/metabolism

abnormal lipid homeostasis ( J:243753 )

♀ • induction of hepatic lipogenesis when fed Western diet

abnormal circulating cholesterol level ( J:243753 )

♀ • both total and free when fed Western diet

increased circulating free fatty acids level ( J:243753 )

♀ • when fed Western diet

increased circulating triglyceride level ( J:243753 )

♀ • when fed Western diet

decreased liver cholesterol level ( J:243753 )

♀ • both total and free when fed Western diet

increased liver free fatty acids level ( J:243753 )

♀ • when fed Western diet

increased liver triglyceride level ( J:243753 )

♀ • when fed Western diet

liver/biliary system

decreased liver cholesterol level ( J:243753 )

♀ • both total and free when fed Western diet

increased liver free fatty acids level ( J:243753 )

♀ • when fed Western diet

increased liver triglyceride level ( J:243753 )

♀ • when fed Western diet

Genotype
MGI:5009547

cn30

• Allelic Composition: Ptpn11^tm1Gsf/Ptpn11^tm1Gsf; Stat3^tm1Vpo/Stat3^tm1Vpo; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

increased circulating alanine transaminase level ( J:172422 )

• increase in serum ALT levels, however ALT levels are lower than in single conditional Ptpn11 mice

increased incidence of tumors by chemical induction ( J:172422 )

• mutants exhibit an increase in hepatocellular carcinoma development after diethylnitrosamine (DEN) injection compared to controls and single conditional Ptpn11 mutants, however tumor frequency and size are similar to that seen in single conditional Stat3 mutants

immune system

liver inflammation ( J:172422 )

• infiltrate of inflammatory cells is seen in the portal triads of livers

• double mutants show less inflammation than seen in single conditional Ptpn11 mice, with reduced size of eosinophilic vacuoles of degeneration in the liver

liver/biliary system

liver inflammation ( J:172422 )

• infiltrate of inflammatory cells is seen in the portal triads of livers

• double mutants show less inflammation than seen in single conditional Ptpn11 mice, with reduced size of eosinophilic vacuoles of degeneration in the liver

neoplasm

increased incidence of tumors by chemical induction ( J:172422 )

• mutants exhibit an increase in hepatocellular carcinoma development after diethylnitrosamine (DEN) injection compared to controls and single conditional Ptpn11 mutants, however tumor frequency and size are similar to that seen in single conditional Stat3 mutants

Genotype
MGI:5897813

cn31

• Allelic Composition: Ccn2^tm1.1Alea/Ccn2^tm1.1Alea; Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz; Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * DBA

liver/biliary system

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

increased liver weight ( J:228499 )

• as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

liver fibrosis ( J:228499 )

• as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

endocrine/exocrine glands

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

growth/size/body

increased liver weight ( J:228499 )

• as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

Genotype
MGI:4819844

cn32

• Allelic Composition: Kras^tm4Tyj/Kras^tm4Tyj; Yap1^tm1.1Dupa/Yap1^tm1.1Dupa; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

neoplasm

increased hepatocellular carcinoma incidence ( J:162628 )

liver/biliary system

increased hepatocellular carcinoma incidence ( J:162628 )

Genotype
MGI:5428898

cn33

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

mortality/aging

premature death ( J:184949 )

• mean survival is 52 weeks of age

neoplasm

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age

• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma

• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas

• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy

• different grades of differentiation are seen in the same tumor

increased metastatic potential ( J:184949 )

• tumors are highly metastatic, with tumors showing invasion into adjacent organs such as the diaphragm, bowel, pancreas and stomach or distant metastasis to the lymph nodes, spleen, lungs, or peritoneal cavity

increased hamartoma incidence ( J:184949 )

• intrahepatic cholangiocarcinoma is associated with biliary hamartomas

cardiovascular system

hemoperitoneum ( J:184949 )

• hepatic lesions frequently show hemorrhage into the peritoneal cavity and exhibit evidence of tumor necrosis

liver/biliary system

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age

• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma

• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas

• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy

• different grades of differentiation are seen in the same tumor

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age

• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma

• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas

• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy

• different grades of differentiation are seen in the same tumor

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrahepatic cholangiocarcinoma		DOID:4928		J:184949

Genotype
MGI:3805348

cn34

• Allelic Composition: Irs1^tm2Tka/Irs1^tm2Tka; Irs2^tm2Tka/Irs2^tm2Tka; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

homeostasis/metabolism

insulin resistance ( J:137846 )

• under fasting and refeeding conditions

immune system

increased susceptibility to autoimmune diabetes ( J:137846 )

• mice develop diabetes

• however, over-expression of a dominant negative Foxo1 by adenoviral transfection improves diabetes

Genotype
MGI:4838529

cn35

• Allelic Composition: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb; Pten^tm1Hwu/Pten^tm1Hwu; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

homeostasis/metabolism

hyperglycemia ( J:160759 )

• about 25-30% increase in fasting glucose levels at 1 month of age

impaired glucose tolerance ( J:160759 )

• glucose intolerance

liver/biliary system

liver/biliary system phenotype ( J:160759 )

N • the liver phenotype observed in single Pten mutants is significantly reduced, with liver weights, triglyceride levels in the liver and fatty liver almost similar to controls

abnormal liver morphology ( J:218587 )

♂ • progenitor cell accumulation in the periductal region of livers occurs later than in single conditional Pten homozygotes, when injury conditions are already present

decreased susceptibility to hepatic steatosis ( J:218587 )

♂ • mice do not show development of steatosis compared to single conditional Pten homozygotes

neoplasm

increased tumor latency ( J:218587 )

♂ • mice exhibit a 6-month delay in liver tumor onset compared to conditional Pten homozygotes

♂ • no mice develop liver tumors between 9 and 12 months of age and 25% of mice older than 12 months develop liver nodules

♂ • however, treatment of 3 month old mice with 3,5-dietoxycarbonyl-1,4 dihydrocollidine (DDC) to induce liver injury leads to massive expansion of hepatic progenitors and development of premalignant lesions

Genotype
MGI:6256732

cn36

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm2Mak/Pten⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

neoplasm

increased cholangiocarcinoma incidence ( J:254370 )

• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression

increased liver tumor incidence ( J:254370 )

• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages

• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation

increased hepatocellular carcinoma incidence ( J:254370 )

• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma

liver/biliary system

increased cholangiocarcinoma incidence ( J:254370 )

• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression

increased liver tumor incidence ( J:254370 )

• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages

• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation

increased hepatocellular carcinoma incidence ( J:254370 )

• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:254370 )

• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression

Genotype
MGI:5428907

cn37

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

mortality/aging

premature death ( J:184949 )

• mean survival is 19 weeks of age

neoplasm

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop intrahepatic cholangiocarcinoma as early as 9 weeks of age

• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas

• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy

• different grades of differentiation are seen in the same tumor

increased metastatic potential ( J:184949 )

• tumors are highly metastatic, with 75% of mutants having tumors showing invasion into adjacent organs such as the diaphragm, bowel, pancreas and stomach or distant metastasis to the lymph nodes, spleen, lungs, or peritoneal cavity

increased hamartoma incidence ( J:184949 )

• intrahepatic cholangiocarcinoma is associated with biliary hamartomas

cardiovascular system

hemoperitoneum ( J:184949 )

• hepatic lesions frequently show hemorrhage into the peritoneal cavity and exhibit evidence of tumor necrosis

liver/biliary system

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop intrahepatic cholangiocarcinoma as early as 9 weeks of age

• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas

• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy

• different grades of differentiation are seen in the same tumor

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop intrahepatic cholangiocarcinoma as early as 9 weeks of age

• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas

• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy

• different grades of differentiation are seen in the same tumor

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrahepatic cholangiocarcinoma		DOID:4928		J:184949

Genotype
MGI:6256730

cn38

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm2Mak/Pten^tm2Mak; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

mortality/aging

premature death ( J:254370 )

• median survival is 46 days

growth/size/body

weight loss ( J:254370 )

• seen in 5 month old mice

postnatal growth retardation ( J:254370 )

distended abdomen ( J:254370 )

• all mice start to show abdominal distension at about 5 weeks of age, frequently accompanied by jaundice and weight loss

• distension is due to hepatic enlargement and/or hemorrhagic ascites

enlarged liver ( J:254370 )

neoplasm

increased cholangiocarcinoma incidence ( J:254370 )

• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma

• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen

• no metastasis or invasion to other organs is seen

• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens

• stellate cells are activated and acquire a myofibroblast-like phenotype

• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct

increased liver tumor incidence ( J:254370 )

• multiple solid tumors with various sizes are seen throughout the liver

• invasive tumors are apparent after 7 weeks of age, with abundant desmoplastic stroma or desmoplasia

endocrine/exocrine glands

bile duct hyperplasia ( J:254370 )

• various degrees of hyperplasia are seen in the bile ducts, characterized by increase in number and size and change in morphology, at 4 weeks of age

• at 5 weeks, a part of the hyperplastic ductal lesions at the hilum become enlarged and show a pattern of papillary growth

increased cholangiocarcinoma incidence ( J:254370 )

• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma

• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen

• no metastasis or invasion to other organs is seen

• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens

• stellate cells are activated and acquire a myofibroblast-like phenotype

• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct

homeostasis/metabolism

hemorrhagic ascites ( J:254370 )

liver/biliary system

bile duct hyperplasia ( J:254370 )

• various degrees of hyperplasia are seen in the bile ducts, characterized by increase in number and size and change in morphology, at 4 weeks of age

• at 5 weeks, a part of the hyperplastic ductal lesions at the hilum become enlarged and show a pattern of papillary growth

increased cholangiocarcinoma incidence ( J:254370 )

• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma

• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen

• no metastasis or invasion to other organs is seen

• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens

• stellate cells are activated and acquire a myofibroblast-like phenotype

• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct

enlarged liver ( J:254370 )

increased liver tumor incidence ( J:254370 )

• multiple solid tumors with various sizes are seen throughout the liver

• invasive tumors are apparent after 7 weeks of age, with abundant desmoplastic stroma or desmoplasia

jaundice ( J:254370 )

• seen in 5 month old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrahepatic cholangiocarcinoma		DOID:4928		J:254370

Genotype
MGI:5618808

cn39

• Allelic Composition: Atp8b1^tm1Nbf/Atp8b1^tm1Nbf; Por^tm1Wolf/Por^tm1Wolf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:215915 )

• mice fed a 0.03% cholic acid-supplemented diet directly from weaning die within a week after the start of the diet

• however, mice fed a 0.03% cholic acid-supplemented diet starting at 4 weeks of age for 4 weeks survive

growth/size/body

weight loss ( J:215915 )

• mice fail to gain weight and even lose weight after starting of 0.03% cholic acid-supplemented diet at 4 weeks of age

increased liver weight ( J:215915 )

• liver weights are increased in mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age do not exhibit fibrosis in the liver

homeostasis/metabolism

increased circulating bilirubin level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit enhanced plasma bilirubin levels

increased circulating alanine transaminase level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit a mild elevation in plasma alanine transaminase levels

increased circulating alkaline phosphatase level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit a mild elevation in plasma alkaline phosphatase levels

abnormal bile salt homeostasis ( J:215915 )

• after 4 weeks on a cholic acid-supplemented diet, plasma bile salts predominantly consist of about 90% taurocholate (TC) and about 7% tauro-beta-muricholate (TbetaMC) and a low concentration of about 0.4% of the secondary bile salt taurochenodeoxycholate (TDC) is seen compared to about 70% TC and 20% TbetaMC in single Atp8b1 homozygotes

• after 4 weeks on a cholic acid-supplemented diet, biliary bile salts predominantly consist of about 90% TC and about 9% TbetaMC compared to 55% TC and 40% TbetaMC in single Atp8b1 homozygotes

• after 4 weeks on a cholic acid-supplemented diet, bile salt hydrophobicity index of plasma is elevated but the hydrophobicity index of bile is unaltered, indicating that the plasma bile salt pool is more hydrophobic

increased bile salt level ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, mice exhibit a strong elevation in plasma bile salt levels

liver/biliary system

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age, exhibit a slight increase in bile duct proliferation

increased liver weight ( J:215915 )

• liver weights are increased in mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age do not exhibit fibrosis in the liver

abnormal bile secretion ( J:215915 )

• after 4 weeks of cholic acid-supplemented diet started at 4 weeks of age, bile flow is strongly (about 3-fold) reduced

• mice, however show normal bile salt output when fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age

cholestasis ( J:215915 )

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age develop a severe cholestatic phenotype with mild liver damage

endocrine/exocrine glands

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 4 weeks starting at 4 weeks of age, exhibit a slight increase in bile duct proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrahepatic cholestasis		DOID:1852		J:215915

Genotype
MGI:3041261

cn40

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

abnormal susceptibility to injury induced morbidity/mortality ( J:89236 )

• mutants are more vulnerable to hepatectomy surgery and most are either moribund or die by 48 hours after surgery

liver/biliary system

liver hemorrhage ( J:89236 )

• mutants develop hemorrhagic liver destruction within the first few hours in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody compared to only minor liver damage in controls

abnormal hepatocyte physiology ( J:89236 )

• primary hepatocytes show reduced phagocytic activity towards bacteria (E.coli) than control cells

increased hepatocyte apoptosis ( J:89236 )

• hepatocytes exhibit increased sensitivity to Fas (Tnfrsf6)-induced apoptosis

impaired liver regeneration ( J:89236 )

• the ability of mutant livers to clear necrotic tissue and to repopulate the injured (by CCl₄ exposure) area by regenerating hepatocytes is impaired

• associated with a persistent inflammatory reaction, overproduction of osteopontin, early and prominent dystrophic calcification, and impaired hepatocyte scattering/migration into diseased areas

liver failure ( J:89236 )

• 80% of mutants die of acute liver failure in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody while controls survive

cardiovascular system

liver hemorrhage ( J:89236 )

• mutants develop hemorrhagic liver destruction within the first few hours in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody compared to only minor liver damage in controls

homeostasis/metabolism

abnormal response to injury ( J:89236 )

• mutants exhibit delayed healing after toxic liver injury induced by CCl₄ exposure

abnormal susceptibility to injury induced morbidity/mortality ( J:89236 )

• mutants are more vulnerable to hepatectomy surgery and most are either moribund or die by 48 hours after surgery

impaired wound healing ( J:89236 )

• hepatocytes fail to migrate in a standard wound healing assay

cellular

increased hepatocyte apoptosis ( J:89236 )

• hepatocytes exhibit increased sensitivity to Fas (Tnfrsf6)-induced apoptosis

Genotype
MGI:5702658

cn41

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * DBA

growth/size/body

enlarged liver ( J:90905 )

• liver is larger in 10 week old mice and further enlarged at 40 weeks

increased liver weight ( J:90905 )

• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks

liver/biliary system

abnormal liver sinusoid morphology ( J:90905 )

• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age

increased hepatocyte proliferation ( J:90905 )

• increase in hepatocyte proliferation at 10 weeks of age

• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age

enlarged liver ( J:90905 )

• liver is larger in 10 week old mice and further enlarged at 40 weeks

increased liver weight ( J:90905 )

• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks

increased liver triglyceride level ( J:90905 )

• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age

• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen

abnormal hepatocyte morphology ( J:90905 )

• hepatocytes acquire expression of an adipocyte-specific marker

Mallory bodies ( J:90905 )

• Mallory bodies are frequently seen in hepatocytes by 40 weeks of age

increased hepatocyte number ( J:90905 )

• absolute numbers of total liver cells are almost normal at 10 weeks of age but increased by 1.5-fold at 40 weeks

microvesicular hepatic steatosis ( J:90905 )

• cytoplasm of liver cells is weakly eosinophilic and contains numerous microvesicular vacuoles containing lipids at 10 weeks of age; vacuolar changes are seen mainly around the central vein

• steatotic changes are more prominent in male than female mice

• by 40 weeks of age, livers show fatty changes of increased severity throughout the hepatic lobule such that aged liver resembles adipocytes in fat tissues

• however, no fibrotic changes are seen in the liver

increased hepatocellular carcinoma incidence ( J:90905 )

• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas

increased liver adenoma incidence ( J:90905 )

• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas

pale liver ( J:90905 )

• livers are light-colored at 10 weeks of age and homogenously white in color at 40 weeks

homeostasis/metabolism

abnormal cellular cholesterol metabolism ( J:90905 )

• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age

decreased fasting circulating glucose level ( J:90905 )

• glucose levels are lower in fasted mutants both before and after oral glucose administration

decreased circulating insulin level ( J:90905 )

• serum insulin levels are reduced at 12 weeks of age

increased circulating alanine transaminase level ( J:90905 )

• serum levels are elevated at 40 weeks of age but not at 10 weeks of age

increased circulating alkaline phosphatase level ( J:90905 )

• serum levels are elevated at 40 weeks of age but not at 10 weeks of age

increased circulating aspartate transaminase level ( J:90905 )

• serum levels are elevated at 40 weeks of age but not at 10 weeks of age

increased insulin sensitivity ( J:90905 )

• intraperitoneal insulin injection reduces glucose levels by a greater amount than in wild-type mice indicating insulin hypersensitivity

increased saturated fatty acids level ( J:90905 )

• 16-carbon monosaturated fatty acids (C16:1) and C18:1 fatty acids are increased in livers of 10 week old mice and C16:0, C16:1, C18:0, C18:1, and C18:2 fatty acids are increased in livers of 40 week old mice

increased liver triglyceride level ( J:90905 )

• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age

• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen

neoplasm

increased hepatocellular carcinoma incidence ( J:90905 )

• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas

increased liver adenoma incidence ( J:90905 )

• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas

increased metastatic potential ( J:90905 )

• 2 mutants with hepatocellular carcinoma show lung metastasis

cardiovascular system

abnormal liver sinusoid morphology ( J:90905 )

• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age

cellular

increased hepatocyte proliferation ( J:90905 )

• increase in hepatocyte proliferation at 10 weeks of age

• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age

abnormal cellular cholesterol metabolism ( J:90905 )

• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age

oxidative stress ( J:90905 )

• hepatic hydrogen peroxide levels in the liver are increased 7-fold, indicating increased production of reactive oxygen species

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:90905
steatotic liver disease		DOID:9452	OMIM:228100	J:90905

Genotype
MGI:5897815

cn42

• Allelic Composition: Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz; Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi}; Yap1^{tm1c(KOMP)Mbp}/Yap1^{tm1c(KOMP)Mbp}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * DBA

liver/biliary system

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells but far less than in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

increased liver weight ( J:228499 )

• much less than in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

liver fibrosis ( J:228499 )

• much less than in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

endocrine/exocrine glands

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells but far less than in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

growth/size/body

increased liver weight ( J:228499 )

• much less than in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

Genotype
MGI:2177363

cn43

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA

normal phenotype

no abnormal phenotype detected ( J:63039 )

• homozygous mice exhibit no discernable phenotype; mice are viable and fertile with normal liver metabolism and normal glucose homeostasis

Genotype
MGI:3805350

cn44

• Allelic Composition: Irs1^tm2Tka/Irs1^tm2Tka; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:137846 )

N • mice exhibit normal hepatic triglyceride content, serum aspartate aminotransferase and alanine aminotransferase indicating a lack of hepatic injury

increased circulating insulin level ( J:137846 )

• mice exhibit higher serum insulin levels 4 and 6 hours after the start of refeeding unlike wild-type mice

insulin resistance ( J:137846 )

• mice exhibit insulin resistance under refeeding conditions

• however, mice do not exhibit insulin resistance under fasting conditions

Genotype
MGI:4417849

cn45

• Allelic Composition: Acsl1^tm1Rcol/Acsl1^tm1Rcol; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

growth/size/body

growth/size/body region phenotype ( J:155714 )

N • normal body weight and organ weights

adipose tissue

adipose tissue phenotype ( J:155714 )

N • normal adiposity

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:155714 )

N • normal plasma levels of metabolites

N • normal golucose tolerance tests and insulin tolerance tests

abnormal lipid homeostasis ( J:155714 )

• liver acyl-CoA levels are 35% lower than controls on a normal diet and 25% lower than controls on a high fat diet

Genotype
MGI:5897811

cn46

• Allelic Composition: Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz; Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi}; Wwtr1^tm1Hku/Wwtr1^tm1Hku; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells but not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

increased liver weight ( J:228499 )

• not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

liver fibrosis ( J:228499 )

• not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

endocrine/exocrine glands

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells but not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

growth/size/body

increased liver weight ( J:228499 )

• not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

Genotype
MGI:5897816

cn47

• Allelic Composition: Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz; Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tgfbr2^tm1Roes/Tgfbr2^tm1Roes
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells but not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

increased liver weight ( J:228499 )

• not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

liver fibrosis ( J:228499 )

• not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

endocrine/exocrine glands

abnormal cholangiocyte morphology ( J:228499 )

• increased immature cholangiocyte-like and oval cells but not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

growth/size/body

increased liver weight ( J:228499 )

• not as much as in Mob1a^tm1.1Asuz/Mob1a^tm1.1Asuz Mob1b^{Gt(CC0690)Wtsi}/Mob1b^{Gt(CC0690)Wtsi} Tg(Alb-cre)21Mgn mice

Genotype
MGI:5912277

cn48

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Smarcd1^tm1.1Jddl/Smarcd1^tm1.1Jddl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

cardiovascular system

decreased susceptibility to atherosclerosis ( J:228944 )

• area of atherosclerotic lesions is reduced by about 53% compared to mice homozygous null for Apoe alone

homeostasis/metabolism

decreased circulating cholesterol level ( J:228944 )

• cholesterol levels are approximately 30% lower in Western diet fed mice compared to diet matched controls

abnormal bile salt homeostasis ( J:228944 )

• expression analysis indicates bile acid metabolism is reduced

Genotype
MGI:5563542

cn49

• Allelic Composition: Hmgb1^tm1.1Ttg/Hmgb1^tm1.1Ttg; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

immune system

increased circulating interleukin-1 beta level ( J:205499 )

• following lipopolysaccharide stimulation

increased circulating interleukin-18 level ( J:205499 )

• following lipopolysaccharide stimulation

homeostasis/metabolism

increased circulating interleukin-1 beta level ( J:205499 )

• following lipopolysaccharide stimulation

increased circulating interleukin-18 level ( J:205499 )

• following lipopolysaccharide stimulation

Genotype
MGI:4819841

cn50

• Allelic Composition: Yap1^tm1.1Dupa/Yap1^tm1.1Dupa; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

growth/size/body

enlarged liver ( J:162628 )

liver/biliary system

increased hepatocyte apoptosis ( J:162628 )

• at 1 to 2 months

increased hepatocyte proliferation ( J:162628 )

abnormal bile duct morphology ( J:162628 )

• after 30 weeks, mice lack bile ducts or bile duct-like structures unlike wild-type mice

abnormal bile duct development ( J:162628 )

• livers fail to form mature bile ducts unlike in wild-type mice

enlarged liver ( J:162628 )

abnormal hepatocyte morphology ( J:162628 )

• at 1 to 2 months, the liver contains multiple areas of injured hepatocytes unlike in wild-type mice

macrovesicular hepatic steatosis ( J:162628 )

liver cirrhosis ( J:162628 )

liver fibrosis ( J:162628 )

• mice exhibit progressive liver fibrosis with early periportal fibrosis at 20 weeks unlike wild-type mice

• at 30 weeks, mice exhibit advanced fibrosis with cirrhosis unlike wild-type mice

pale liver ( J:162628 )

homeostasis/metabolism

increased circulating bilirubin level ( J:162628 )

increased circulating alanine transaminase level ( J:162628 )

endocrine/exocrine glands

abnormal bile duct morphology ( J:162628 )

• after 30 weeks, mice lack bile ducts or bile duct-like structures unlike wild-type mice

abnormal bile duct development ( J:162628 )

• livers fail to form mature bile ducts unlike in wild-type mice

cellular

increased hepatocyte apoptosis ( J:162628 )

• at 1 to 2 months

increased hepatocyte proliferation ( J:162628 )

Genotype
MGI:4819842

cn51

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Yap1^tm1.1Dupa/Yap1^tm1.1Dupa; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:162628 )

N • liver is as enlarge as in Nf2^tm2Gth/Nf2^tm2Gth Tg(Alb-cre)21Mgn mice

N • bile over-proliferation observed in Nf2^tm2Gth/Nf2^tm2Gth Tg(Alb-cre)21Mgn mice is suppressed

neoplasm

neoplasm ( J:162628 )

N • mice do not develop bile duct hamartomas or hepatocellular carcinoma unlike Nf2^tm2Gth/Nf2^tm2Gth Tg(Alb-cre)21Mgn mice

Genotype
MGI:4819843

cn52

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Yap1^tm1.1Dupa/Yap1⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:162628 )

N • mice do not exhibit bile duct proliferation

enlarged liver ( J:162628 )

• slightly

neoplasm

neoplasm ( J:162628 )

N • mice do not develop bile duct hamartomas or hepatocellular carcinoma

growth/size/body

enlarged liver ( J:162628 )

• slightly

Genotype
MGI:4819845

cn53

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

bile duct hyperplasia ( J:162628 )

bile duct proliferation ( J:162628 )

abnormal liver morphology ( J:162628 )

• at E18.5, multiple tubular structures surround each portal vein unlike in wild-type mice

enlarged liver ( J:162628 )

increased hepatobiliary system tumor incidence ( J:162628 )

• mice exhibit widespread bile duct hamartomas that expand into the deep liver parenchyma unlike wild-type mice

increased hepatocellular carcinoma incidence ( J:162628 )

• at 1 year of age

neoplasm

increased hepatobiliary system tumor incidence ( J:162628 )

• mice exhibit widespread bile duct hamartomas that expand into the deep liver parenchyma unlike wild-type mice

increased hepatocellular carcinoma incidence ( J:162628 )

• at 1 year of age

endocrine/exocrine glands

bile duct hyperplasia ( J:162628 )

bile duct proliferation ( J:162628 )

growth/size/body

enlarged liver ( J:162628 )

Genotype
MGI:3826674

cn54

• Allelic Composition: Cyb5a^tm1Wolf/Cyb5a^tm1Wolf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism

abnormal xenobiotic pharmacokinetics ( J:143097 )

• early (0 to 60 minutes) concentrations of a drug mixture, which contains midazolam, phenacetin, metaprodol, chlorzoxazone and tolbutamide, administered intravenously are higher than in wild-type mice

• at 2 hours, concentrations of the drug mixture administered intravenously was lower than in wild-type mice

• mice exhibit faster drug clearance and AUC (except in the case of midazolam) compared to wild-type mice

• the half-lives of phenacetin, tolbutamide, chlorzozane and midazolam are longer than in wild-type mice

• metabolite production following administration of drugs intravenously is shifted to the right compared to in wild-type mice

• when the drug mixture is given orally, AUC, Cmax are higher and clearance is slower than in wild-type mice for midazolam, phenacetin and metoprolol

• AUC and Cmax for tolbutamide given orally are lower than in wild-type mice

• when tolbutamide is administered orally or intravenously on its own, AUC and Cmax are increased and clearance is decreased compared to in wild-type mice

• mice exhibit a 4-fold increase in bioavailability of orally administered midazolam compared to in wild-type mice

• mice exhibit a 50% decrease in bioavailability of tolbutamide when delivered in a mixture and a 100% increase in bioavailability when administered on its own compared to in wild-type mice

liver/biliary system

liver/biliary system phenotype ( J:143097 )

N • liver morphology is normal

Genotype
MGI:5444453

cn55

• Allelic Composition: Hsd11b1^tm1Ggla/Hsd11b1^tm1Ggla; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:189059 )

N • when fed a high fat diet, mice exhibit normal insulin resistance

N • mice fed a high fat diet exhibit normal hepatic lipid accumulation

decreased circulating corticosterone level ( J:189059 )

decreased circulating insulin level ( J:189059 )

• mice fed a high fat diet exhibit less of an increase in insulin levels compared with control mice

increased circulating HDL cholesterol level ( J:189059 )

• when fed a low fat diet

• however, there is no significant difference when mice are fed a high fat diet

abnormal glucose tolerance ( J:189059 )

• mice fed a high fat diet resist glucose intolerance with enhanced glucose clearance compared with control mice

behavior/neurological

abnormal eating behavior ( J:189059 )

• marginally reduced when fed normal chow

endocrine/exocrine glands

enlarged adrenal glands ( J:189059 )

growth/size/body

growth/size/body region phenotype ( J:189059 )

N • whether fed a low fat or high fat diet, mice exhibit normal weight

liver/biliary system

liver/biliary system phenotype ( J:189059 )

N • mice fed a high fat diet exhibit normal hepatic lipid accumulation

Genotype
MGI:3620636

cn56

• Allelic Composition: Keap1^tm1Mym/Keap1^tm2Mym; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

mortality/aging

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:103791 )

• unlike most wild-type mice, mutant mice survive following intraperitoneal administration of 600-mg or 700-mg acetaminophen/kg body weight

homeostasis/metabolism

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:103791 )

• unlike most wild-type mice, mutant mice survive following intraperitoneal administration of 600-mg or 700-mg acetaminophen/kg body weight

decreased physiological sensitivity to xenobiotic ( J:103791 )

• much milder hepatic injury in livers of mutant mice following acetaminophen exposure

Genotype
MGI:3620114

cn57

• Allelic Composition: Rr27^tm2Msb/Rr27⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

cellular

paternal imprinting ( J:105567 )

• paternal allele specific methylation is maintained

• maternal Igf2 allele expression is detected in the neonate liver

• paternal Igf2 allele expression is reduced

Genotype
MGI:3806986

cn58

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

liver/biliary system

liver inflammation ( J:138099 )

• at 10 weeks of age

abnormal liver morphology ( J:138099 )

• by 40 weeks of age, livers contain Mallory bodies, ballooning hepatocytes and accumulation of lobular inflammatory cells

enlarged liver ( J:138099 )

• beginning at 10 weeks of age, mice exhibit enlargement of the liver that progressed further by 40 weeks of age

increased liver cholesterol level ( J:138099 )

• at 10 and 40 weeks of age

increased liver triglyceride level ( J:138099 )

• at 10 and 40 weeks of age

abnormal hepatocyte morphology ( J:138099 )

• at 10 weeks of age, the cytoplasm of hepatocytes contain lipid-filled micro- and macro-vesicular vacuoles unlike in wild-type mice

• at 40 weeks of age, micro- and macro-vesicular vacuoles coalesce to and displace the nucleus

Mallory bodies ( J:138099 )

• by 40 weeks of age, livers contain Mallory bodies

hepatic steatosis ( J:138099 )

• at 10 weeks of age

increased hepatocellular carcinoma incidence ( J:138099 )

• at 74 to 78 weeks of age, 83% of males and 50% of females exhibit hepatocellular carcinomas that develop within liver adenomas and contain fewer lipid droplets than the adenomas

• 2 of 6 mice exhibit metastasis of hepatocellular carcinomas to the lungs

increased liver adenoma incidence ( J:138099 )

• at 40 weeks of age, 66% of males and 30% of females exhibit liver adenomas that contain large lipid droplets

liver fibrosis ( J:138099 )

• at 40 weeks of age

pale liver ( J:138099 )

• beginning at 10 weeks of age, mice exhibit a pale liver that is white by 40 weeks of age

abnormal hepatocyte physiology ( J:220381 )

• the polyploid mononuclear hepatocyte population is enriched in the liver of 3 and 10 month old mutants

• highly polyploid hepatocytes are also present in hepatocellular tumors in the livers

increased hepatocyte proliferation ( J:138099 )

• at 10 weeks of age, hepatocyte proliferation is increased while apoptosis rates are normal

neoplasm

increased hepatocellular carcinoma incidence ( J:138099 )

• at 74 to 78 weeks of age, 83% of males and 50% of females exhibit hepatocellular carcinomas that develop within liver adenomas and contain fewer lipid droplets than the adenomas

• 2 of 6 mice exhibit metastasis of hepatocellular carcinomas to the lungs

increased liver adenoma incidence ( J:138099 )

• at 40 weeks of age, 66% of males and 30% of females exhibit liver adenomas that contain large lipid droplets

homeostasis/metabolism

increased circulating alanine transaminase level ( J:138099 )

• at 40 weeks of age

increased circulating alkaline phosphatase level ( J:138099 )

• at 40 weeks of age

increased liver cholesterol level ( J:138099 )

• at 10 and 40 weeks of age

increased liver triglyceride level ( J:138099 )

• at 10 and 40 weeks of age

immune system

liver inflammation ( J:138099 )

• at 10 weeks of age

cellular

increased hepatocyte proliferation ( J:138099 )

• at 10 weeks of age, hepatocyte proliferation is increased while apoptosis rates are normal

growth/size/body

enlarged liver ( J:138099 )

• beginning at 10 weeks of age, mice exhibit enlargement of the liver that progressed further by 40 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:138099

Genotype
MGI:5009548

cn59

• Allelic Composition: Stat3^tm1Vpo/Stat3^tm1Vpo; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:172422 )

• mutants exhibit an increase in hepatocellular carcinoma development (increase in tumor number and size) after diethylnitrosamine (DEN) injection compared to controls

neoplasm

increased incidence of tumors by chemical induction ( J:172422 )

• mutants exhibit an increase in hepatocellular carcinoma development (increase in tumor number and size) after diethylnitrosamine (DEN) injection compared to controls

Genotype
MGI:4461042

cn60

• Allelic Composition: Map3k7^tm1Aki/Map3k7^tm1Aki; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

liver/biliary system

increased hepatocyte proliferation ( J:160521 )

abnormal bile duct morphology ( J:160521 )

• mice exhibit areas of ductopenia within some portal tracts unlike wild-type mice

abnormal hepatocyte morphology ( J:160521 )

focal hepatic necrosis ( J:160521 )

homeostasis/metabolism

increased circulating bilirubin level ( J:160521 )

• mild

endocrine/exocrine glands

abnormal bile duct morphology ( J:160521 )

• mice exhibit areas of ductopenia within some portal tracts unlike wild-type mice

cellular

increased hepatocyte proliferation ( J:160521 )

Genotype
MGI:2656921

cn61

• Allelic Composition: Por^tm2Wolf/Por^tm1Wolf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

growth/size/body

enlarged liver ( J:82951 )

• liver almost doubled in size

homeostasis/metabolism

decreased circulating cholesterol level ( J:82951 )

• 65% reduction in serum cholesterol

decreased circulating triglyceride level ( J:82951 )

• 50% reduction in serum triglyceride level

increased circulating alanine transaminase level ( J:82951 )

abnormal bile salt level ( J:82951 )

• 90% reduction in bile acid volume in the gall bladder

abnormal xenobiotic pharmacokinetics ( J:82951 )

• altered metabolism of pentobarbital and acetominophen

abnormal acetaminophen metabolism ( J:82951 )

liver/biliary system

enlarged liver ( J:82951 )

• liver almost doubled in size

macrovesicular hepatic steatosis ( J:82951 )

• macrovesicular fatty changes

microvesicular hepatic steatosis ( J:82951 )

• microvesicular fatty changes

pale liver ( J:82951 )

reproductive system

reduced fertility ( J:82951 )

• reduced fertility when mated with other null animals

decreased litter size ( J:82951 )

• reduced litter size when mated with other null animals

Genotype
MGI:2656922

cn62

• Allelic Composition: Por^tm1Wolf/Por^tm1Wolf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

growth/size/body

enlarged liver ( J:82951 )

• liver almost doubled in size

homeostasis/metabolism

decreased circulating cholesterol level ( J:82951 )

• 65% reduction in serum cholesterol level

decreased circulating triglyceride level ( J:82951 )

• 50% reduction in serum triglyceride level

increased circulating alanine transaminase level ( J:82951 )

abnormal bile salt level ( J:82951 )

• 90% reduction in bile acid volume in the gall bladder

abnormal xenobiotic pharmacokinetics ( J:82951 )

• abnormal metabolism of acetaminophen and pentobarbital

abnormal acetaminophen metabolism ( J:82951 )

liver/biliary system

enlarged liver ( J:82951 )

• liver almost doubled in size

macrovesicular hepatic steatosis ( J:82951 )

• macrovesicular fatty changes

microvesicular hepatic steatosis ( J:82951 )

• microvesicular fatty changes

pale liver ( J:82951 )

reproductive system

reduced fertility ( J:82951 )

• reduced fertility when mated with other null animals

decreased litter size ( J:82951 )

• reduced litter size when mated with other null animals

Genotype
MGI:5618809

cn63

• Allelic Composition: Abcb4^tm1Bor/Abcb4^tm1Bor; Por^tm1Wolf/Por^tm1Wolf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA * FVB/N

endocrine/exocrine glands

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit bile duct proliferation

growth/size/body

growth/size/body region phenotype ( J:215915 )

N • mice fed a 0.03% cholic acid-supplemented diet directly from weaning exhibit normal growth

increased liver weight ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit an increased liver to body weight ratio

cellular

increased hepatocyte proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit increased hepatocyte proliferation

homeostasis/metabolism

increased circulating bilirubin level ( J:215915 )

• plasma bilirubin levels are mildly increased at weaning and are further increased after 8 weeks of 0.03% cholic acid-supplemented diet

increased circulating alanine transaminase level ( J:215915 )

• plasma alanine transaminase levels are strongly elevated after 8 weeks of cholic acid-supplemented diet

increased circulating alkaline phosphatase level ( J:215915 )

• plasma alkaline phosphatase levels are strongly elevated after 8 weeks of cholic acid-supplemented diet

abnormal bile salt homeostasis ( J:215915 )

• on a cholic acid-supplemented diet, plasma bile salts predominantly consist of about 90% taurocholate (TC) and about 7% tauro-beta-muricholate (TbetaMC) compared to about 60% TC and 23% TbetaMC in single Abcb4 homozygotes

• on a cholic acid-supplemented diet, biliary bile salts predominantly consist of about 90% TC and about 2.5% of the secondary bile salt taurochenodeoxycholate (TDC) compared to 75% TC and 20% TbetaMC in single Abcb4 homozygotes

• on a cholic acid-supplemented diet, the biliary hydrophobicity index, but not the plasma hydrophobicity index, is elevated, indicating a more hydrophobic biliary bile salt pool

• however, mice fed a cholic acid-supplemented diet for 8 weeks exhibit normal bile flow and biliary bile salt output

increased bile salt level ( J:215915 )

• plasma bile salt levels are strongly elevated after 8 weeks of cholic acid-supplemented diet

liver/biliary system

increased hepatocyte proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit increased hepatocyte proliferation

bile duct proliferation ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit bile duct proliferation

increased liver weight ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit an increased liver to body weight ratio

liver fibrosis ( J:215915 )

• mice fed a regular diet exhibit portal fibrosis

• mice fed a cholic acid-supplemented diet for 8 weeks exhibit portal fibrosis that is more severe than in single Abcb4 homozygotes

cholestasis ( J:215915 )

• mice fed a cholic acid-supplemented diet for 8 weeks develop a severe cholestatic phenotype with severe liver damage

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrahepatic cholestasis		DOID:1852		J:215915

Genotype
MGI:5523090

cn64

• Allelic Composition: Abhd5^tm1.1Lqyu/Abhd5^tm1.1Lqyu; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * DBA

growth/size/body

enlarged liver ( J:199570 )

♂ • more obvious over time

increased liver weight ( J:199570 )

♂

liver/biliary system

abnormal liver morphology ( J:199570 )

♂ • pale, yellowish, hardened with rare small white nodules

♂ • severe liver damage at 42 weeks

♂ • however, hepatic mitochondrial cholesterol content is normal

enlarged liver ( J:199570 )

♂ • more obvious over time

increased liver weight ( J:199570 )

♂

increased liver cholesterol level ( J:199570 )

♂ • of total cholesterol at 16 weeks and more so at 42 weeks

♂ • of free cholesterol and cholesterol ester in the liver at 42 weeks

increased liver free fatty acids level ( J:199570 )

♂ • 2- to 14-fold at 12 weeks

increased liver triglyceride level ( J:199570 )

♂ • 8-fold at 16 weeks

♂ • 52-fold at 42 weeks

abnormal hepatocyte morphology ( J:199570 )

♂ • foamy hepatocytes more so at 42 weeks than 16 weeks, resulting from accumulation of many small vacuoles in a hepatocyte

hepatic steatosis ( J:199570 )

♂ • small and large vacuoles at 16 and 42 weeks

♂ • progressive steatohepatitis

macrovesicular hepatic steatosis ( J:199570 )

• macrovesicular steatosis primarily located in the zone 1 and panlobular region

microvesicular hepatic steatosis ( J:199570 )

• microvesicular steatosis predominantly around zones 3 and 2

liver fibrosis ( J:199570 )

♂ • progressive

pale liver ( J:199570 )

♂

abnormal liver physiology ( J:199570 )

♂ • increased hepatic oxidative stress at 42 weeks

♂ • however, hepatic endoplasmic reticulum stress is normal

liver inflammation ( J:199570 )

♂ • progressive steatohepatitis

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:199570 )

♂N • mice exhibit normal VLDL triglyceride and plasma lipids

♂N • mice exhibit normal insulin sensitivity

decreased fatty acid oxidation ( J:199570 )

♂ • reduced fatty acid oxidation in the liver

increased circulating alanine transaminase level ( J:199570 )

♂ • at 42 weeks

increased circulating aspartate transaminase level ( J:199570 )

♂

abnormal lipid level ( J:199570 )

♂ • a few fatty acid species of diacylglycerol are decreased in the liver

increased liver cholesterol level ( J:199570 )

♂ • of total cholesterol at 16 weeks and more so at 42 weeks

♂ • of free cholesterol and cholesterol ester in the liver at 42 weeks

increased liver free fatty acids level ( J:199570 )

♂ • 2- to 14-fold at 12 weeks

abnormal phospholipid level ( J:199570 )

♂ • decreased hepatic phospholipid at 42, but not 16, weeks

increased liver triglyceride level ( J:199570 )

♂ • 8-fold at 16 weeks

♂ • 52-fold at 42 weeks

decreased triglyceride lipase activity ( J:199570 )

♂ • reduced triglyceride hydrolase activity in the liver at 16 and 42 weeks

immune system

liver inflammation ( J:199570 )

♂ • progressive steatohepatitis

cellular

decreased fatty acid oxidation ( J:199570 )

♂ • reduced fatty acid oxidation in the liver

oxidative stress ( J:199570 )

♂ • increased hepatic oxidative stress at 42 weeks

Genotype
MGI:3578950

cn65

• Allelic Composition: Gab1^tm1Gsf/Gab1^tm1Gsf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism

abnormal glucose homeostasis ( J:98318 )

decreased circulating glucose level ( J:98318 )

• blood glucose levels are reduced in homozygotes from 9.1 to 28.9% in both the fed and fasted states compared to sex- and age-matched wild-type mice

decreased circulating insulin level ( J:98318 )

• serum insulin levels are reduced at 2 months and 1 year of age

improved glucose tolerance ( J:98318 )

• both glucose injection and glucose clamp assays indicate improved glucose tolerance

decreased glycogen level ( J:98318 )

• glycogen levels are reduced in 1 year old mutants; however circulating glyconeogenic precursor levels are normal

increased insulin sensitivity ( J:98318 )

• peripheral and hepatic insulin sensitivity are increased

abnormal lipid homeostasis ( J:98318 )

decreased circulating free fatty acids level ( J:98318 )

• free fatty acid plasma levels are mildly reduced

decreased circulating triglyceride level ( J:98318 )

• retention of triglycerides in the liver is increased and circulating levels are decreased

Genotype
MGI:3805708

cn66

• Allelic Composition: Pdss2^tm1Dalg/Pdss2^tm1Dalg; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism

abnormal mitophagy ( J:136670 )

• increased autophagy of mitochondria

abnormal circulating cholesterol level ( J:136670 )

• elevated plasma cholesterol

abnormal energy homeostasis ( J:136670 )

• many biochemical pathways involved in energy production are upregulated

cellular

abnormal mitophagy ( J:136670 )

• increased autophagy of mitochondria

abnormal aerobic respiration ( J:136670 )

• impaired mitochondrial respiration

abnormal respiratory electron transport chain ( J:136670 )

• significant decrease in complex I and complex II-dependent respiratory chain capacity in liver

Genotype
MGI:5009546

cn67

• Allelic Composition: Ptpn11^tm1Gsf/Ptpn11^tm1Gsf; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

growth/size/body

weight loss ( J:172422 )

• aged mutants become leaner by 10.7% for males and 14.9% for females, with a significant decrease of their body weights at 1 year of age

liver hyperplasia ( J:172422 )

• lobular architecture of the liver is distorted by the development of hyperplastic hepatocyte plates

homeostasis/metabolism

increased circulating interleukin-6 level ( J:172422 )

increased circulating alanine transaminase level ( J:172422 )

• serum levels of alanine aminotransferase are higher than in controls

increased circulating aspartate transaminase level ( J:172422 )

• serum levels of aspartate aminotransferase are higher than in controls

increased incidence of tumors by chemical induction ( J:172422 )

• injection of a single dose of diethylnitrosamine (DEN) on P15 results in an increase in the number and size of (hepatocellular carcinoma) liver tumors in mutants compared to controls

immune system

increased circulating interleukin-6 level ( J:172422 )

increased acute inflammation ( J:172422 )

• intraperitoneal LPS injection elicits a stronger liver damage response in mutants than in controls as indicated by higher serum alanine aminotransferase levels

• mutants show a 130% increase in spleen size 14 days after LPS challenge as compared to 98% increase in controls indicating increased systemic inflammatory response

• mutants show increased inflammatory cell infiltration into hepatic parenchyma after LPS challenge

• circulating IL-6 and TNFalpha levels are increased following LPS injection

• LPS stimulation of isolated hepatocytes results in increased IL-6 secretion by mutant hepatocytes compared to controls

liver inflammation ( J:172422 )

• 93% of mutant livers contain areas with infiltrate of inflammatory cells, concentrating around the portal triads with extension into the parenchyma

• necrotic zones of livers are always associated with inflammatory cells, whereas inflammation is occasionally observed without necrosis

• 8 of 19 aged mutants develop focal microgranuloma consisting of mononuclear inflammatory cells

liver/biliary system

increased hepatocyte proliferation ( J:172422 )

liver inflammation ( J:172422 )

• 93% of mutant livers contain areas with infiltrate of inflammatory cells, concentrating around the portal triads with extension into the parenchyma

• necrotic zones of livers are always associated with inflammatory cells, whereas inflammation is occasionally observed without necrosis

• 8 of 19 aged mutants develop focal microgranuloma consisting of mononuclear inflammatory cells

abnormal liver morphology ( J:172422 )

• one or several foci of pallor are noticeable on the liver surface of 34% of analyzed mutants

• beginning at 5 months of age, regenerative foci are noticeable in the liver and nodular regenerative hyperplasia is seen from 8 months of age

• hepatic inflammation and necrosis, leading to nodular regenerative hyperplasia

liver hyperplasia ( J:172422 )

• lobular architecture of the liver is distorted by the development of hyperplastic hepatocyte plates

abnormal liver parenchyma morphology ( J:172422 )

• hepatic parenchyma shows regenerative hyperplasia, with 13 of 19 livers having nodule formation

• the space between hepatocytes is reduced inside the nodules

abnormal hepatocyte morphology ( J:172422 )

• massive hepatocyte degeneration is seen inside of or surrounding the hyperplastic nodules, in association with vacuoles containing eosinophilic material, but not in the liver parenchyma

hepatic necrosis ( J:172422 )

• liver shows small focal areas as well as large areas of parenchymal necrosis, with necrosis observed in 47% of mutants

focal hepatic necrosis ( J:172422 )

• liver shows small focal areas of parenchymal necrosis

increased liver adenoma incidence ( J:172422 )

• from 12-18 months of age, one or a few hepatocellular adenomas are frequently seen in mutants; tumors bulge from the liver surface, are often paler than the hepatic parenchyma, but sometimes darker or red when accompanied by bleeding

• tumors are unencapsulated, well delimited and show expanding masses of hepatocytes

liver fibrosis ( J:172422 )

• fibrosis is seen at the portal triads but not near the necrosis or into the parenchyma

neoplasm

increased incidence of tumors by chemical induction ( J:172422 )

• injection of a single dose of diethylnitrosamine (DEN) on P15 results in an increase in the number and size of (hepatocellular carcinoma) liver tumors in mutants compared to controls

increased liver adenoma incidence ( J:172422 )

• from 12-18 months of age, one or a few hepatocellular adenomas are frequently seen in mutants; tumors bulge from the liver surface, are often paler than the hepatic parenchyma, but sometimes darker or red when accompanied by bleeding

• tumors are unencapsulated, well delimited and show expanding masses of hepatocytes

cellular

increased hepatocyte proliferation ( J:172422 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular adenoma		DOID:0050868		J:172422

Genotype
MGI:5475096

cn68

• Allelic Composition: Ei24^tm1Hzha/Ei24^tm1Hzha; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

Hepatomegaly and tumor-like protrusions in the liver of Ei24^tm1Hzha/Ei24^tm1Hzha Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

homeostasis/metabolism

impaired autophagy ( J:193420 )

• impaired autophagic flux in the liver at 3 months

liver/biliary system

abnormal liver morphology ( J:193420 )

• by 10 months, livers exhibit multiple tumor-like protusions with no signs of malignancy

enlarged liver ( J:193420 )

• by 3 months

abnormal liver lobule morphology ( J:193420 )

• disorganized hepatic lobules

abnormal hepatocyte morphology ( J:193420 )

• swollen hepatocytes with swollen mitochondria

abnormal hepatocyte mitochondrial morphology ( J:193420 )

• swollen

growth/size/body

enlarged liver ( J:193420 )

• by 3 months

cellular

abnormal hepatocyte mitochondrial morphology ( J:193420 )

• swollen

impaired autophagy ( J:193420 )

• impaired autophagic flux in the liver at 3 months

Genotype
MGI:3851810

cn69

• Allelic Composition: Pex5^tm1Pec/Pex5^tm1Pec; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

growth/size/body

decreased body weight ( J:112503 )

• 30-40% lower than controls by 7 weeks of age

abnormal postnatal growth ( J:112503 )

• low body weight recovers to near normal between 7 weeks and 3 months

slow postnatal weight gain ( J:112503 )

• growth retardation starting about the third week after birth

enlarged liver ( J:112503 )

• hepatomegaly at 10 weeks

liver hyperplasia ( J:112503 )

• hypertrophic and hyperplastic hepatocytes particularly in pericentric region

liver/biliary system

liver/biliary system phenotype ( J:112503 )

N • mice appear healthy and fertile with normal liver function through 14 months of age

abnormal liver morphology ( J:112503 )

• possible compression of liver sinusoids

enlarged liver ( J:112503 )

• hepatomegaly at 10 weeks

liver hyperplasia ( J:112503 )

• hypertrophic and hyperplastic hepatocytes particularly in pericentric region

increased liver tumor incidence ( J:112503 )

• increased incidence after 12 months

cellular

abnormal cell morphology ( J:112503 )

• in the liver

abnormal endoplasmic reticulum morphology ( J:112503 )

• proliferation of smooth endoplasmic reticulum

abnormal mitochondrial inner membrane morphology ( J:112503 )

• tubulation of inner membrane

abnormal mitochondrial crista morphology ( J:112503 )

• reduced numbers of curled and stacked cristae

abnormal mitochondrial shape ( J:112503 )

• proliferation of pleomorphic mitochondria

• mitochondria are normal if catalase positive peroxisomes are present

abnormal lysosome morphology ( J:112503 )

• groups of lysoosomes as well as lipid drops observed

abnormal respiratory electron transport chain ( J:112503 )

• impaired respiratory chain

abnormal mitochondrial ATP synthesis coupled electron transport ( J:112503 )

• activity of mitchondrial complex II and IV are normal in the liver

• activity of mitochondrial complex I is less than 15% of normal in the liver at 20 weeks of age

• activity of citochondria complex III and V about 40% normal

• reduced membrane potential of liver mitochondria

• reduced ATP production

abnormal fatty acid beta-oxidation ( J:121804 )

• beta oxidation in cultured hepatocytes is abnormal

homeostasis/metabolism

abnormal fatty acid beta-oxidation ( J:121804 )

• beta oxidation in cultured hepatocytes is abnormal

abnormal blood homeostasis ( J:112503 )

• whole blood pyruvate slightly decreased

increased circulating lactate level ( J:112503 )

• whole blood lactate is increased about 70%

abnormal glucose homeostasis ( J:112503 )

• increased activity of the glycolytic pathway

abnormal bile salt homeostasis ( J:121804 )

• bile acid metabolism is considerably reduced

neoplasm

increased liver tumor incidence ( J:112503 )

• increased incidence after 12 months

Genotype
MGI:3805306

cn70

• Allelic Composition: Irs1^tm1Mfw/Irs1^tm1Mfw; Irs2^tm2Mfw/Irs2^tm2Mfw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

increased circulating glucose level ( J:137845 )

• fasting and postprandial

hyperglycemia ( J:137845 )

• by 5 weeks of age

increased circulating insulin level ( J:137845 )

• fasting and postprandial

decreased circulating cholesterol level ( J:137845 )

decreased circulating HDL cholesterol level ( J:137845 )

decreased circulating free fatty acids level ( J:137845 )

impaired glucose tolerance ( J:137845 )

decreased liver glycogen level ( J:137845 )

insulin resistance ( J:137845 )

abnormal triglyceride level ( J:137845 )

decreased circulating triglyceride level ( J:137845 )

• at 3 months of age, triglyceride secretion is decreased 60% compared to in wild-type mice

liver/biliary system

decreased liver glycogen level ( J:137845 )

immune system

increased susceptibility to autoimmune diabetes ( J:137845 )

• mice develop diabetes

growth/size/body

decreased body size ( J:137845 )

Genotype
MGI:3032498

cn71

• Allelic Composition: Adar^tm1Knk/Adar^tm1Knk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

Increased apoptosis in liver of Adar^tm1Knk/Adar^tm1Knk Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

hematopoietic system

hematopoietic system phenotype ( J:87714 )

N • no observed hematopoietic defects

homeostasis/metabolism

hyperglycemia ( J:87714 )

abnormal circulating enzyme level ( J:87714 )

• increased levels of enzymes indicating hepatocellular damage

increased circulating alanine transaminase level ( J:87714 )

increased circulating alkaline phosphatase level ( J:87714 )

increased circulating aspartate transaminase level ( J:87714 )

increased circulating lactate dehydrogenase level ( J:87714 )

liver/biliary system

increased hepatocyte apoptosis ( J:87714 )

• increased apoptosis among hepatocytes

abnormal liver morphology ( J:87714 )

• disorganized liver architecture at 6 weeks of age

cellular

increased hepatocyte apoptosis ( J:87714 )

• increased apoptosis among hepatocytes

growth/size/body

decreased body size ( J:87714 )

• body size about 50-70% of controls

Genotype
MGI:4439272

cn72

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

liver/biliary system

abnormal hepatocyte physiology ( J:158299 )

• hepatocytes exhibit decreased VLDL binding, uptake, and degradation compared with wild-type cells

Genotype
MGI:5566667

cn73

• Allelic Composition: Mtch2^tm2Atgr/Mtch2^tm2.1Atgr; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

liver/biliary system

liver failure ( J:209127 )

• resistant to liver failure caused by intraperitoneal injection of anti-FAS antibody

• recruitment of tBID to liver mitochondria is reduced

Genotype
MGI:3805308

cn74

• Allelic Composition: Irs1^tm1Mfw/Irs1^tm1Mfw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

impaired glucose tolerance ( J:137845 )

• mild

Genotype
MGI:4949418

cn75

• Allelic Composition: Ern1^tm1Rjk/Ern1^tm2.1Rjk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

liver/biliary system

increased hepatocyte apoptosis ( J:171230 )

• 5-times in response to Bortezomib treatment

increased liver triglyceride level ( J:171230 )

• following tamoxifen treatment

• following partial hepatectomy

• in response to Bortezomib treatment

abnormal hepatocyte morphology ( J:171230 )

• liver cells exhibit less rough endoplasmic reticulum content compared with control liver cells

hepatic steatosis ( J:171230 )

• mice exhibit a slight increase in hepatic lipid content compared with control mice

• mice subjected to liver stress (partial hepatectomy or treatment with tamoxifen or Bortezomib) exhibit increased accumulation of lipids in the liver compared with control mice

• however, phospholipid synthesis is normal

homeostasis/metabolism

abnormal lipid level ( J:171230 )

• mice exhibit a slight increase in hepatic lipid content compared with control mice

• mice subjected to liver stress (partial hepatectomy or treatment with tamoxifen or Bortezomib) exhibit increased accumulation of lipids in the liver compared with control mice

• however, phospholipid levels in the liver are normal

decreased circulating cholesterol level ( J:171230 )

• following tamoxifen-treatment

increased liver triglyceride level ( J:171230 )

• following tamoxifen treatment

• following partial hepatectomy

• in response to Bortezomib treatment

abnormal apolipoprotein level ( J:171230 )

• following tamoxifen-treatment, secretion of apolipoproteins from liver cells is decreased compared to in control mice

cellular

increased hepatocyte apoptosis ( J:171230 )

• 5-times in response to Bortezomib treatment

Genotype
MGI:5448536

cn76

• Allelic Composition: Mir122^tm1.2Kgh/Mir122⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

neoplasm

increased hepatocellular carcinoma incidence ( J:190067 )

• in 2 of 6 mice at 20 months

liver/biliary system

increased hepatocellular carcinoma incidence ( J:190067 )

• in 2 of 6 mice at 20 months

Genotype
MGI:5448537

cn77

• Allelic Composition: Mir122^tm1.2Kgh/Mir122^tm1.2Kgh; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

Abnormal liver structure in Mir122^tm1.2Kgh/Mir122^tm1.2Kgh Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

endocrine/exocrine glands

bile duct proliferation ( J:190067 )

• increased

homeostasis/metabolism

increased circulating interleukin-6 level ( J:190067 )

♂ • in tumor-bearing male mice

abnormal circulating enzyme level ( J:190067 )

• increase in serum gamma-glutamyl transpeptidase

increased circulating alanine transaminase level ( J:190067 )

• in tumor-bearing mice

increased circulating alkaline phosphatase level ( J:190067 )

• 2-fold as early as 5 weeks of age

• in tumor-bearing mice

decreased liver glycogen level ( J:190067 )

• 2.5-fold at 8 to 10 weeks of age

• at 6 months of age

abnormal lipid homeostasis ( J:190067 )

• mice exhibit a small increase in de novo triglyceride synthesis compared with control mice

decreased circulating cholesterol level ( J:190067 )

• as early as 5 weeks of age

decreased circulating HDL cholesterol level ( J:190067 )

• as early as 5 weeks of age

decreased circulating LDL cholesterol level ( J:190067 )

• as early as 5 weeks of age

increased bile salt level ( J:190067 )

• in tumor-bearing mice

increased liver triglyceride level ( J:190067 )

• 2.5-fold at 8 to 10 weeks of age

• at 6 months of age

liver/biliary system

bile duct proliferation ( J:190067 )

• increased

decreased liver glycogen level ( J:190067 )

• 2.5-fold at 8 to 10 weeks of age

• at 6 months of age

increased liver triglyceride level ( J:190067 )

• 2.5-fold at 8 to 10 weeks of age

• at 6 months of age

microvesicular hepatic steatosis ( J:190067 )

increased liver tumor incidence ( J:190067 )

♂ • at 12 to 17 months, 13 of 26 male mice develop liver tumors

increased hepatocellular carcinoma incidence ( J:190067 )

♀ • in 2 of 20 mice at 12 to 17 months of age

liver fibrosis ( J:190067 )

abnormal liver physiology ( J:190067 )

• mice exhibit a small increase in de novo triglyceride synthesis and reduced triglyceride secretion in the liver compared with control mice

liver inflammation ( J:190067 )

• steatohepatitis with bridging fibrosis

• recruitment of monocytes and neutrophils to the liver

abnormal oval cell physiology ( J:190067 )

• increased proliferation

neoplasm

increased liver tumor incidence ( J:190067 )

♂ • at 12 to 17 months, 13 of 26 male mice develop liver tumors

increased hepatocellular carcinoma incidence ( J:190067 )

♀ • in 2 of 20 mice at 12 to 17 months of age

immune system

increased neutrophil cell number ( J:190067 )

• 3-fold in the liver at 10 months

increased monocyte cell number ( J:190067 )

• 3-fold in the liver at 10 months

increased circulating interleukin-6 level ( J:190067 )

♂ • in tumor-bearing male mice

increased interleukin-6 secretion ( J:190067 )

♂ • from monocytes and neutrophils in the liver

increased tumor necrosis factor secretion ( J:190067 )

• from monocytes and neutrophils in the liver

liver inflammation ( J:190067 )

• steatohepatitis with bridging fibrosis

• recruitment of monocytes and neutrophils to the liver

hematopoietic system

increased neutrophil cell number ( J:190067 )

• 3-fold in the liver at 10 months

increased monocyte cell number ( J:190067 )

• 3-fold in the liver at 10 months

Genotype
MGI:3805307

cn78

• Allelic Composition: Irs2^tm2Mfw/Irs2^tm2Mfw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:137845 )

N • mice exhibit normal glucose metabolism

Genotype
MGI:6376140

cn79

• Allelic Composition: Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(tetO-Xbp1_is)#Pesch/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB

adipose tissue

decreased total body fat amount ( J:194290 )

• doxycycline (Dox)-treated mice show a gradual reduction in the volume of adipose tissue

• when mice are taken off the Dox-containing diet, the fat tissue volume increases

homeostasis/metabolism

increased circulating free fatty acids level ( J:194290 )

• increase in serum free fatty acids in the fed state after 72 hours of induction with Dox

• however, Dox-treated mice maintain the same rate of fatty acid and cholesterol synthesis as controls in a biochemical assay for de novo lipid synthesis

increased respiratory quotient ( J:194290 )

• mice fed a doxycycline (Dox)-containing diet show a higher respiratory exchange ratio than wild-type mice during the dark phase

abnormal glucose homeostasis ( J:194290 )

• mice exhibit a reduction in hepatic glucose release when exposed to Dox for 48 hours

• metabolic cage studies indicate higher glucose utilization in Dox-treated mice

decreased fasting circulating glucose level ( J:194290 )

• a 6-hour fast causes severe hypoglycemia within 48 hours after induction with Dox

hypoglycemia ( J:194290 )

• serum glucose levels start to decrease by 72 hours after induction with Dox under fed conditions

• administration of a PPAR-alpha agonist exacerbates the hypoglycemia in Dox-treated mice

decreased circulating insulin level ( J:194290 )

• fed insulin levels start to decrease upon induction with Dox and are significantly lower by 72 hours of induction

• 96 hours after Dox-induction, fasted insulin levels are lower

decreased liver glycogen level ( J:194290 )

• hepatic glycogen is severely depleted after 48 hours of induction with Dox

increased insulin sensitivity ( J:194290 )

• livers of Dox-treated mice show a faster response to insulin exposure and isolated hepatocytes induced with Dox show an enhanced insulin response indicating hepatic insulin sensitivity

increased liver triglyceride level ( J:194290 )

• hepatic triglyceride content is increased in Dox-treated mice

• a 6-hour fast increases liver triglyceride content acutely within 24 hours of Dox exposure

enhanced lipolysis ( J:194290 )

• the fasting effects of adipocyte lipolysis on hepatic triglyceride content are exacerbated in Dox-treated mice compared to wild-type mice

liver/biliary system

abnormal liver morphology ( J:194290 )

• liver mass is increased 1.7-fold within 48 hours of induction with Dox

• Dox-treated mice show reduced dry mass content per wet liver

• increase in total liver protein in Dox-treated mice

decreased liver glycogen level ( J:194290 )

• hepatic glycogen is severely depleted after 48 hours of induction with Dox

increased liver triglyceride level ( J:194290 )

• hepatic triglyceride content is increased in Dox-treated mice

• a 6-hour fast increases liver triglyceride content acutely within 24 hours of Dox exposure

hepatic steatosis ( J:194290 )

• Dox-treated mice show an increase in hepatic lipid levels

• when mice are taken off the Dox-containing diet, the liver steatosis decreases rapidly

Genotype
MGI:3805304

cn80

• Allelic Composition: Foxo1^tm1Rdp/Foxo1^tm1Rdp; Irs1^tm1Mfw/Irs1^tm1Mfw; Irs2^tm2Mfw/Irs2^tm2Mfw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:137845 )

N • unlike in Irs1 and Irs2 double null mice, fasting glucose, insulin, and adiponectin levels, insulin resistance, fed glucose levels, hepatic glycogen levels, and glucose tolerance are normal

decreased circulating cholesterol level ( J:137845 )

decreased circulating HDL cholesterol level ( J:137845 )

• mice exhibit a partial recovery of plasma HDL cholesterol levels compared to in Irs1 and Irs2 double knockout mice

decreased circulating free fatty acids level ( J:137845 )

abnormal triglyceride level ( J:137845 )

• triglyceride secretion is decreased compared to in wild-type mice but increased compared to in Irs1 and Irs2 double knockout mice

decreased circulating triglyceride level ( J:137845 )

Genotype
MGI:4430357

cn81

• Allelic Composition: Irs1^tm1Mfw/Irs1⁺; Irs2^tm2Mfw/Irs2^tm2Mfw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N

homeostasis/metabolism

impaired glucose tolerance ( J:156999 )

• significantly glucose intolerant

Genotype
MGI:4430358

cn82

• Allelic Composition: Irs1^tm2.1Mfw/Irs1^tm2.1Mfw; Irs2^tm2Mfw/Irs2^tm2Mfw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N

homeostasis/metabolism

increased circulating insulin level ( J:156999 )

• fasting insulin concentration are elevated

impaired glucose tolerance ( J:156999 )

• significantly glucose intolerant

Genotype
MGI:4430356

cn83

• Allelic Composition: Irs1^tm1Mfw/Irs1^tm2.1Mfw; Irs2^tm2Mfw/Irs2^tm2Mfw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N

homeostasis/metabolism

increased circulating insulin level ( J:156999 )

• fasting and fed insulin concentrations are elevated

impaired glucose tolerance ( J:156999 )

• severe glucose intolerance

insulin resistance ( J:156999 )

• significant insulin resistance

Genotype
MGI:3778811

cn84

• Allelic Composition: Notch2^tm3Grid/Notch2^tm3.1Grid; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA

liver/biliary system

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

focal hepatic necrosis ( J:133171 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:133171 )

N • blood urea nitrogen levels are normal

increased circulating bilirubin level ( J:133171 )

• in some mice

increased circulating alanine transaminase level ( J:133171 )

• in some mice

increased circulating alkaline phosphatase level ( J:133171 )

• in some mice

growth/size/body

decreased body size ( J:133171 )

decreased body weight ( J:133171 )

• at P8 to P9, mice are 19% lighter than wild-type

• at 4 to 5 weeks of age, mice are 15% lighter than wild-type

endocrine/exocrine glands

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

Genotype
MGI:3704087

cn85

• Allelic Composition: Por^tm1Ding/Por⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:84422 )

• at 2 months of age, mice have ~25% of normal activity levels toward NKK and AP, and HO activity is below 5% compared to controls

Genotype
MGI:5485021

cn86

• Allelic Composition: Aqp11^tm1.1Nlsn/Aqp11^tm1.1Nlsn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:194939 )

N • mice exhibit normal glucose homeostasis under fed, fasted and re-fed conditions

decreased blood urea nitrogen level ( J:194939 )

• in unchallenged mice

decreased circulating ketone body level ( J:194939 )

• in unchallenged and fasted mice

increased circulating HDL cholesterol level ( J:194939 )

• in unchallenged mice

decreased circulating free fatty acids level ( J:194939 )

• in fasted mice

decreased circulating glycerol level ( J:194939 )

• in fasted mice

decreased circulating triglyceride level ( J:194939 )

• in fasted mice

increased circulating aspartate transaminase level ( J:194939 )

• in fasted mice

liver/biliary system

abnormal hepatocyte morphology ( J:194939 )

• following a 24 h fast, hepatocytes surrounding the portal veins are more eosinophilic with vacuolization than in perivenous hepatocytes unlike in control mice

• re-fed mice exhibit rapid and variable development of giant vacuoles (dilated rough endoplasmic reticulum) in periportal hepatocytes unlike in control mice

• orally administration of casein to fasted mice exhibit vacuolization of periportal hepatocytes unlike in control mice

• administration of amino acids to fasted mice exhibit varying degrees of hepatocyte vacuolization depending on the amino acid (glutamine, glutamate, glycine>alanine>arginine>lysine) unlike in control mice

• fasted mice treated with ammonium acetate or pyruvate exhibit some degree of vacuolization unlike control mice

• however, oral administration of glucose, urea or triglyceride to fasted mice does not induce vacuolization

cellular

abnormal endoplasmic reticulum morphology ( J:194939 )

• dilated in the hepatocytes of mice that were fasted and re-fed

Genotype
MGI:2668453

cn87

• Allelic Composition: Por^tm1Ding/Por^tm1Ding; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA

liver/biliary system

abnormal liver morphology ( J:84422 )

• hepatocellular swelling without lipidosis, characterized by abundant, lightly granular, pale, eosinophilic cytoplasm, is observed in some animals

increased liver weight ( J:84422 )

• liver weight/body weight ratio is significantly increased in males and females, with no significant change in body weight observed

hepatic necrosis ( J:84422 )

• individual hepatocyte necrosis or apoptosis, and a few scattered foci of necrosis are seen, sometimes with secondary neutrophilic infiltrates, in some livers

hepatic steatosis ( J:84422 )

pale liver ( J:84422 )

• liver is lighter red in color compared to normal liver

homeostasis/metabolism

decreased circulating cholesterol level ( J:84422 )

• at 3 weeks of age, plasma total cholesterol is decreased 30% compared to controls and is decreased 80% at 2 months of age

abnormal enzyme/coenzyme activity ( J:84422 )

• liver microsomal NADPH-cytochrome P450 activity toward cytochrome c, NKK, and acetominophen (AP), as well heme oxygenase (HO) activity are decreased in mice at 3 weeks

• at 2 months of age, mice have 5-8% of normal activity levels toward NKK and AP, and barely detectable HO activity

behavior/neurological

enhanced behavioral response to xenobiotic ( J:84422 )

• mice are still unconscious 10 h after a single 60 mg/kg dose of pentobarbital, unlike controls which regained righting reflex after about 30 min

growth/size/body

increased liver weight ( J:84422 )

• liver weight/body weight ratio is significantly increased in males and females, with no significant change in body weight observed

Genotype
MGI:3778812

cn88

• Allelic Composition: Notch2^tm2Grid/Notch2^tm3Grid; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA

liver/biliary system

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

focal hepatic necrosis ( J:133171 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:133171 )

N • blood urea nitrogen levels are normal

increased circulating bilirubin level ( J:133171 )

• in some mice

increased circulating alanine transaminase level ( J:133171 )

• in some mice

increased circulating alkaline phosphatase level ( J:133171 )

• in some mice

growth/size/body

decreased body size ( J:133171 )

decreased body weight ( J:133171 )

• at P8 to P9, mice are 19% lighter than wild-type

• at 4 to 5 weeks of age, mice are 15% lighter than wild-type

endocrine/exocrine glands

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

Genotype
MGI:3805303

cn89

• Allelic Composition: Foxo1^tm1Rdp/Foxo1^tm1Rdp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA * FVB

homeostasis/metabolism

improved glucose tolerance ( J:137845 )

Genotype
MGI:5499118

cn90

• Allelic Composition: Pros1^tm1Grl/Pros1^tm1Grl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6 * DBA

mortality/aging

mortality/aging ( J:198769 )

N • mice appear grossly normal at E17.5 and adult mice are viable

cardiovascular system

cardiovascular system phenotype ( J:198769 )

N • clot-containing blood vessels are well-organized and normal in appearance with intact structure

homeostasis/metabolism

abnormal thrombosis ( J:198769 )

• focal fibrin deposits detected in blood vessels at E15.5 to E17.5 with vascular occlusion or hemorrhage

Genotype
MGI:6515760

cn91

• Allelic Composition: Polr2m^tm1.1Rgr/Polr2m^tm1.1Rgr; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA

liver/biliary system

increased hepatocyte apoptosis ( J:291184 )

• dramatically increased by 8 weeks of age

increased hepatocyte proliferation ( J:291184 )

• expression analysis indicates more cells have re-entered the cell cycle and at 8 weeks of age the number of Ki67 positive hepatocytes is further increased

abnormal liver morphology ( J:291184 )

• liver architecture is distorted with the pericentral expression pattern of glutamine synthetase absent

abnormal hepatocyte morphology ( J:291184 )

• increased size with some being extremely enlarged and containing more than 3 nuclei indicating incomplete mitoses

cellular

increased hepatocyte apoptosis ( J:291184 )

• dramatically increased by 8 weeks of age

increased hepatocyte proliferation ( J:291184 )

• expression analysis indicates more cells have re-entered the cell cycle and at 8 weeks of age the number of Ki67 positive hepatocytes is further increased

Genotype
MGI:3821875

cn92

• Allelic Composition: Ncor1^tm1Anh/Ncor1^tm1Anh; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6 * DBA

homeostasis/metabolism

decreased circulating thyroxine level ( J:142045 )

• male mice exhibit a slight decrease in plasma T4 levels compared to in Ncor1^tm1Anh control mice

decreased circulating LDL cholesterol level ( J:142045 )

• PTU treated mice exhibit decreased serum LDL cholesterol levels compared to in similarly treated Ncor1^tm1Anh control mice

Genotype
MGI:2176966

cn93

• Allelic Composition: Vhl^tm1Jae/Vhl^tm1Jae; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA

Vascular tumors in Vhl^tm1.1Jae/Vhl⁺ livers and vascular lesions in Vhl^tm1Jae/Vhl^tm1Jae Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

mortality/aging

premature death ( J:67505 )

• die between 6 and 13 weeks of age

growth/size/body

decreased body weight ( J:67505 )

• body weight is about 50% of wild-type

enlarged liver ( J:67505 )

• severe

liver/biliary system

abnormal liver morphology ( J:67505 )

• numerous blood filled vascular cavities, but no large cavernous hemangiomas, are seen

enlarged liver ( J:67505 )

• severe

hepatic steatosis ( J:67505 , J:97652 )

• accumulation of neutral fats in hepatocytes is detectable by 2 weeks of age (J:67505)

• severe steatosis (J:97652)

cardiovascular system

abnormal blood vessel morphology ( J:67505 )

• foci of increased vascularization are present in the liver

increased vascular endothelial cell number ( J:97652 )

• proliferation of endothelial cells in hepatic blood vessels

abnormal vasodilation ( J:97652 )

• hepatic vascular angiectasia

hematopoietic system

polycythemia ( J:67505 )

muscle

abnormal vasodilation ( J:97652 )

• hepatic vascular angiectasia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:67505 , J:97652

Genotype
MGI:6791351

cn94

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J

homeostasis/metabolism

hyperglycemia ( J:234643 )

• at 2 months of age, mice show hyperglycemia in the fed state

• however, blood glucose levels become normal by 6 months of age

increased circulating insulin level ( J:234643 )

• at 2 months of age, mice show hyperinsulinemia in the fed state that is more severe than in Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

impaired glucose tolerance ( J:234643 )

• at 2 months of age, mice show severe glucose intolerance

• surprisingly, glucose intolerance is not severe at 6 months of age

decreased liver glycogen level ( J:234643 )

• at 2 months of age, liver glycogen levels are decreased to a greater extent than in Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

insulin resistance ( J:234643 )

• at 2 months of age, mice show severe insulin intolerance

• surprisingly, insulin intolerance is not severe at 6 months of age

abnormal enzyme/coenzyme activity ( J:234643 )

• insulin treatment fails to stimulate glycogen synthase activity in hepatocytes, unlike in wild-type hepatocytes

liver/biliary system

abnormal liver morphology ( J:234643 )

• at 2 months of age, males show scattered focal dysplasia in the periportal area of the liver

• however, overall liver architecture is normal

decreased liver glycogen level ( J:234643 )

• at 2 months of age, liver glycogen levels are decreased to a greater extent than in Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

abnormal liver physiology ( J:234643 )

• insulin receptor (IR) autophosphorylation and activating phosphorylation of AKT (pT308) are significantly reduced whereas inhibitory phosphorylation of GSK3 (pS9) is modestly reduced in whole-liver lysates from insulin-treated mice

abnormal hepatocyte physiology ( J:234643 )

• insulin-dependent glycogen synthase (GS) activation is abolished in hepatocytes

Genotype
MGI:5427456

cn95

• Allelic Composition: Pnpla2^tm1Gam/Pnpla2^tm1Gam; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * DBA

growth/size/body

increased liver weight ( J:185116 )

• at 3 months

homeostasis/metabolism

decreased fatty acid oxidation ( J:185116 )

• decreased fatty acid oxidation in the liver

increased circulating free fatty acids level ( J:185116 )

• after 48 hours of fasting

increased circulating alanine transaminase level ( J:185116 )

• without a change in macrophage numbers, fibrosis or apoptosis

increased liver triglyceride level ( J:185116 )

• at 3 months

decreased basal metabolism ( J:185116 )

• heat production after 48 hours of fasting is lower than in wild-type mice

liver/biliary system

abnormal cholangiocyte morphology ( J:185116 )

• cholangiocytes contain lipid droplets unlike in wild-type mice

increased liver weight ( J:185116 )

• at 3 months

increased liver triglyceride level ( J:185116 )

• at 3 months

abnormal hepatocyte morphology ( J:185116 )

• increase in size and number of hepatocyte lipid droplets

• increased lipolysosomes

macrovesicular hepatic steatosis ( J:185116 )

• progressive macrovesicular steatosis

microvesicular hepatic steatosis ( J:185116 )

• pericentral microvesicular steatosis

cellular

decreased fatty acid oxidation ( J:185116 )

• decreased fatty acid oxidation in the liver

endocrine/exocrine glands

abnormal cholangiocyte morphology ( J:185116 )

• cholangiocytes contain lipid droplets unlike in wild-type mice

Genotype
MGI:6157296

cn96

• Allelic Composition: Fbxw7^tm1Iken/Fbxw7^tm1Iken; Kras^tm4Tyj/Kras⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6N * DBA

liver/biliary system

increased cholangiocarcinoma incidence ( J:258194 )

• all mice develop cholangiocarcinoma-like lesions composed of dysplastic dust-like structures surrounded by fibrosis within 2 months of birth

neoplasm

increased cholangiocarcinoma incidence ( J:258194 )

• all mice develop cholangiocarcinoma-like lesions composed of dysplastic dust-like structures surrounded by fibrosis within 2 months of birth

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:258194 )

• all mice develop cholangiocarcinoma-like lesions composed of dysplastic dust-like structures surrounded by fibrosis within 2 months of birth

Genotype
MGI:6157295

cn97

• Allelic Composition: Fbxw7^tm1Iken/Fbxw7⁺; Kras^tm4Tyj/Kras⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6N * DBA

endocrine/exocrine glands

bile duct hyperplasia ( J:258194 )

• bile duct hyperplasia is seen in some mice at 8 months of age

dilated bile duct ( J:258194 )

• bile duct dilation is seen in some mice at 8 months of age

liver/biliary system

bile duct hyperplasia ( J:258194 )

• bile duct hyperplasia is seen in some mice at 8 months of age

dilated bile duct ( J:258194 )

• bile duct dilation is seen in some mice at 8 months of age

Genotype
MGI:5428897

cn98

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

neoplasm

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop invasive intrahepatic cholangiocarcinoma with low penetrance (1 of 8 mutants) and long latency (at 36 weeks of age)

increased liver tumor incidence ( J:254370 )

• mice develop liver tumors at 12 months of age and do not show obvious symptoms up to 18 months of age

• tumors resemble hepatocellular dysplasia

liver/biliary system

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop invasive intrahepatic cholangiocarcinoma with low penetrance (1 of 8 mutants) and long latency (at 36 weeks of age)

increased liver tumor incidence ( J:254370 )

• mice develop liver tumors at 12 months of age and do not show obvious symptoms up to 18 months of age

• tumors resemble hepatocellular dysplasia

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:184949 )

• mutants develop invasive intrahepatic cholangiocarcinoma with low penetrance (1 of 8 mutants) and long latency (at 36 weeks of age)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrahepatic cholangiocarcinoma		DOID:4928		J:184949

Genotype
MGI:3832405

cn99

• Allelic Composition: Vhl^tm1Jae/Vhl^tm1Jae; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

mortality/aging

premature death ( J:144666 )

• mice die at 6 to 8 weeks of age

liver/biliary system

increased hepatocyte proliferation ( J:144666 )

abnormal liver morphology ( J:144666 )

• at 6 weeks, the liver is friable and stippled with irregular yellow spots on a reddish black background unlike in wild-type mice

• hepatic vascularity is increased compared to in wild-type mice

increased liver weight ( J:144666 )

• at 6 weeks of age

abnormal hepatocyte morphology ( J:144666 )

• livers contain irregular, dilated, blood filled sinusoids and cytoplasmic vacuolizations within hepatocytes with eccentric nuclei unlike in wild-type mice

hepatic steatosis ( J:144666 )

• in a mixed micro- and macrovesicular steatotic pattern

hematopoietic system

increased hematocrit ( J:144666 )

reticulocytosis ( J:144666 )

cardiovascular system

abnormal blood vessel morphology ( J:144666 )

• hepatic vascularity is increased compared to in wild-type mice

growth/size/body

decreased body size ( J:144666 )

• mice are runted

increased liver weight ( J:144666 )

• at 6 weeks of age

integument

reddish skin ( J:144666 )

• of paws and unfurred skin by 4 to 6 weeks of age

cellular

increased hepatocyte proliferation ( J:144666 )

Genotype
MGI:4829790

cn100

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

liver/biliary system

increased hepatocyte apoptosis ( J:218587 )

♂ • progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age

increased hepatocyte proliferation ( J:218587 )

♂ • at 12 months of age, livers show increased cell proliferation

increased cholangiocarcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

abnormal liver morphology ( J:218587 )

♂ • progressive and chronic liver injury that begins before proliferation of hepatic progenitors

♂ • accumulation of hepatic progenitor cells in the periductal region of livers from 9-12 months of age

♂ • liver shows multiple layers of progenitor cells surrounding a single layer of ductal cells which show high mitotic activity after 9 months of age

enlarged liver ( J:88441 , J:171445 )

• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age (J:171445)

• mutants treated with rapamycin show reduced hepatocyte cell size, thus reducing the liver:body weight ratio (J:171445)

increased liver weight ( J:88441 , J:160759 )

increased liver glycogen level ( J:88441 )

• increase in glycogen storage in the liver

increased liver triglyceride level ( J:88441 , J:160759 )

• 3-fold increase in triglyceride content in the liver (J:88441)

• however, normal levels of plasma triglycerides (J:88441)

• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively (J:160759)

hepatic steatosis ( J:88441 , J:160759 , J:218587 )

• progressive development of fatty liver (J:88441)

♂ (J:218587)

macrovesicular hepatic steatosis ( J:171445 )

• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age

• mutants treated with rapamycin exhibit no differences in steatosis compared to vehicle-treated mutants

increased liver tumor incidence ( J:218587 )

♂ • mice develop liver tumors starting at approximately 8-9 months of age

♂ • 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age

♂ • tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells

increased hepatocellular carcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

pale liver ( J:88441 )

adipose tissue

decreased total body fat amount ( J:88441 )

• 50% reduction in total body fat content

homeostasis/metabolism

decreased circulating glucose level ( J:88441 )

• decrease in fasting glucose levels at 1 and 3 months of age, however at 6 months of age, when severe steatosis is seen, the fasting glucose level is similar to wild-type

decreased circulating insulin level ( J:88441 )

• decrease in fasting plasma insulin levels at 3 and 6 months of age

decreased circulating leptin level ( J:88441 )

• decrease in serum leptin levels at one month of age

• however eating behavior is normal

increased circulating alanine transaminase level ( J:218587 )

♂ • serum alanine aminotransferase levels increase progressively, reaching 5-fold higher levels at 12 months of age

improved glucose tolerance ( J:88441 )

• increase in glucose clearance during an intraperitoneal glucose load

increased liver glycogen level ( J:88441 )

• increase in glycogen storage in the liver

increased insulin sensitivity ( J:88441 )

• increase in insulin sensitivity in the liver

abnormal fatty acids level ( J:88441 )

• hepatocyte fatty acid uptake by passive diffusion is increased by 20% compared to controls, however active transportation of fatty acid is not changed and thus total fatty acid uptake is not significantly altered

• rate of fatty acid synthesis is 2.5-fold higher in mutant livers than in controls

decreased circulating free fatty acids level ( J:88441 )

• 30% decrease in circulating free fatty acids

increased liver triglyceride level ( J:88441 , J:160759 )

• 3-fold increase in triglyceride content in the liver (J:88441)

• however, normal levels of plasma triglycerides (J:88441)

• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively (J:160759)

impaired lipolysis ( J:88441 )

• decrease in lipolysis rate

growth/size/body

enlarged liver ( J:88441 , J:171445 )

• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age (J:171445)

• mutants treated with rapamycin show reduced hepatocyte cell size, thus reducing the liver:body weight ratio (J:171445)

increased liver weight ( J:88441 , J:160759 )

cellular

increased hepatocyte apoptosis ( J:218587 )

♂ • progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age

increased hepatocyte proliferation ( J:218587 )

♂ • at 12 months of age, livers show increased cell proliferation

oxidative stress ( J:218587 )

♂ • marker analysis indicates oxidative stress in the liver

neoplasm

increased cholangiocarcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

increased liver tumor incidence ( J:218587 )

♂ • mice develop liver tumors starting at approximately 8-9 months of age

♂ • 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age

♂ • tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells

increased hepatocellular carcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:218587 )

♂ • tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:218587
steatotic liver disease		DOID:9452	OMIM:228100	J:216841

Genotype
MGI:3805349

cn101

• Allelic Composition: Irs2^tm2Tka/Irs2^tm2Tka; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:137846 )

N • mice exhibit normal hepatic triglyceride content, serum aspartate aminotransferase and alanine aminotransferase indicating a lack of hepatic injury

increased circulating insulin level ( J:137846 )

• mice exhibit higher serum insulin levels 24 hours after fasting and 30 and 60 minutes after the start of refeeding unlike wild-type mice

insulin resistance ( J:137846 )

• mice exhibit insulin resistance under fasting conditions

• however, mice do not exhibit insulin resistance under refeeding conditions

Genotype
MGI:5529807

cn102

• Allelic Composition: Ccn1^tm3.1Lfl/Ccn1^tm3.1Lfl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:204032 )

N • mice exhibit normal liver morphology and outcome after partial hepatectomy

liver fibrosis ( J:204032 )

• CCl4-treated mice exhibit prominent central-to-central bridging fibrosis and a 4-fold increase more fibrotic area of collagen deposition in hydroxyproline accumulation compared with control mice

• 3 weeks following bile duct ligation, mice exhibit a 3-fold increase in fibrotic area compared with wild-type mice

homeostasis/metabolism

increased susceptibility to injury ( J:204032 )

• CCl4-treated mice exhibit prominent central-to-central bridging fibrosis, a 4-fold increase more fibrotic area of collagen deposition, 3-fold increase in hydroxyproline accumulation and fewer senescence cells around the central vein compared with control mice

• 3 weeks following bile duct ligation, mice exhibit a 3-fold increase in fibrotic area and hydroxyproline content and fewer senescent cells compared with wild-type mice

• however, CCl4-treated mice exhibit normal level of liver damage (serum alanine aminotransferase, cell proliferation and cell apoptosis) and myofibroblast apoptosis

cellular

abnormal cellular replicative senescence ( J:204032 )

• fewer senescence cells surrounding the hepatic central veins in CCl4-treated mice

Genotype
MGI:6236292

cn103

• Allelic Composition: Rraga^tm2Dmsa/Rraga^tm2Dmsa; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

homeostasis/metabolism

decreased circulating glucose level ( J:213516 )

• mild reduction in ad libitum blood glucose levels in young mice

increased insulin sensitivity ( J:213516 )

• increased reduction in glycaemia following injection of insulin in an insulin tolerance test

Genotype
MGI:5009705

cn104

• Allelic Composition: Tsc1^tm1Djk/Tsc1^tm1Djk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

homeostasis/metabolism

abnormal homeostasis ( J:171445 )

• gene expression analysis indicates that fat utilization and glucose production are promoted in mutants

decreased circulating triglyceride level ( J:171445 )

• plasma triglyceride levels are lower than in wild-type mice, however adiponectin and leptin levels are no different

• mutants do not show an increase in plasma triglyceride levels in response to the high-fat diet as is seen in wild-type mice

impaired glucose tolerance ( J:171445 )

• mutants exhibit mild but significant glucose intolerance

insulin resistance ( J:171445 )

• mutants exhibit a slight reduction in systemic insulin sensitivity

• insulin levels at 30 minutes following glucose administration are higher in mutants than controls, indicating insulin resistance

• however, fasting plasma glucose and insulin levels are normal

liver/biliary system

liver/biliary system phenotype ( J:171445 )

N • mutants normally do not exhibit hepatic steatosis, however when fed a high-fat diet and treated with rapamycin, they develop steatosis and show increased levels of hepatic triglycerides

enlarged liver ( J:171445 )

• mutants develop hepatomegaly

abnormal hepatocyte morphology ( J:171445 )

• increase in hepatocyte cell size

abnormal hepatocyte physiology ( J:171445 )

• hepatocytes are resistant to steatosis induced by a high-fat diet

growth/size/body

enlarged liver ( J:171445 )

• mutants develop hepatomegaly

Genotype
MGI:3775382

cn105

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

premature death ( J:121640 )

• 82% of mice die by 6 weeks of age with some mice surviving a few weeks longer

homeostasis/metabolism

decreased insulin secretion ( J:121640 )

hyperglycemia ( J:121640 )

• mice develop hypoglycemia at 2 weeks of age that rapidly worsens by 6 weeks of age

• mice exhibit high fasting glucose serum levels

increased circulating insulin level ( J:121640 )

impaired glucose tolerance ( J:121640 )

insulin resistance ( J:121640 )

endocrine/exocrine glands

decreased insulin secretion ( J:121640 )

renal/urinary system

polyuria ( J:121640 )

• during terminal stages

behavior/neurological

polydipsia ( J:121640 )

• during terminal stages

digestive/alimentary system

digestive/alimentary phenotype ( J:121640 )

N • unlike mice null for Insr in beta cells mice, islet cell mass is not increased despite similar levels of elevated insulin levels

growth/size/body

decreased body weight ( J:121640 )

• mice develop severe diabetes and loss 30% of their body weight in terminal stages

Genotype
MGI:3775385

cn106

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

homeostasis/metabolism

decreased circulating glucose level ( J:121640 )

• at 10 to 12 months of age

hyperglycemia ( J:121640 )

• while mice display normoglycemia during the first 3 weeks of life, at 4 weeks mice develop hypoglycemia that lasts until week 6

increased circulating insulin level ( J:121640 )

impaired glucose tolerance ( J:121640 )

insulin resistance ( J:121640 )

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:121640 )

• at 2 weeks beta cell mass is increased 2-fold and at 6 weeks 4-fold compared to in wild-type mice due to increased mitosis of beta cells

• at 10 to 12 months of age, mice exhibit a 27-fold increase in beta cell mass due to an 8-fold increase in proliferating beta cells with a slight increase in apoptosis

Genotype
MGI:3583116

cn107

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Pdx1^tm1Ted/Pdx1⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:92861 )

• these mutants fail to exhibit an adaptive islet hyperplastic response to insulin resistance; instead, pancreatic beta cell mass is reduced, and islets appear small with scattered non-beta cells

Genotype
MGI:3664093

cn108

• Allelic Composition: Ptpn1^tm2Bbk/Ptpn1^tm2Bbk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

growth/size/body

growth/size/body region phenotype ( J:111969 )

N • mice with liver-specific Ptpn1 deletion show similar body weight to Ptpn1-sufficient controls

Genotype
MGI:3839859

cn109

• Allelic Composition: Gt(ROSA)26Sor^{tm2(sb11)Njen}/Gt(ROSA)26Sor⁺; Trp53^tm3Tyj/Trp53⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; TgTn(sb-T2/Onc)68Dla/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2 * FVB/N

neoplasm

increased hepatocellular carcinoma incidence ( J:147264 )

• seen in older males

increased liver adenoma incidence ( J:147264 )

• tumor formation is more prevalent and starts earlier in males compared to females

liver/biliary system

abnormal liver morphology ( J:147264 )

• preneoplastic nodules are first detected at about 160 days of age in males

• liver nodules in quadruple transgenic mice are larger and more numerous compared to triple transgenic mice that are wild-type at the Trp53 locus

increased hepatocellular carcinoma incidence ( J:147264 )

• seen in older males

increased liver adenoma incidence ( J:147264 )

• tumor formation is more prevalent and starts earlier in males compared to females

Genotype
MGI:6189551

cn110

• Allelic Composition: Sephs1^tm1.1Dhat/Sephs1^tm1.1Dhat; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

homeostasis/metabolism

decreased liver iron level ( J:245139 )

decreased liver manganese level ( J:245139 )

abnormal enzyme/coenzyme activity ( J:245139 )

• reduced aspartate transaminase activity

liver/biliary system

decreased liver iron level ( J:245139 )

decreased liver manganese level ( J:245139 )

Genotype
MGI:3039262

cn111

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * DBA/2 * FVB

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:63878 )

• at 6 months, mutant mice show a 50% increase in alkaline phosphatase levels, suggesting biliary tract dysfunction

increased circulating aspartate transaminase level ( J:63878 )

• at 6 months, mutant mice show a 2.6-fold increase in aspartate aminotransferase levels, suggesting hepatocellular damage

• in contrast, no significant changes in levels of lactate dehydrogenase or alanine aminotransferase are observed

abnormal circulating serum albumin level ( J:63878 )

• at 6 months, mutant mice display a 50% reduction in serum albumin levels

abnormal glucose homeostasis ( J:63878 )

• at 2 months, male mutants fail to suppress hepatic glucose output in response to insulin administration, despite intact insulin signaling in adipose tissue and nearly normal insulin signaling in muscle

increased insulin secretion ( J:63878 )

♀ • at 6 months, female mutants show a have 5- to 6-fold increase in pancreatic insulin content measured in acid-ethanol extracts

hyperglycemia ( J:63878 )

♂ • at 2 months, male mutants exhibit significantly elevated blood glucose in the fed state, despite a 20-fold increase in insulin levels relative to control mice; in contrast, glucagon levels remain unaffected

♂ • at 2 months, male mutants also display a mild hyperglycemia in the fasted state, despite a 7-fold increase in serum insulin levels

♂ • unexpectedly, as mutant mice age, the elevated fasting blood glucose levels progressively decline; by 6 months of age, mutants exhibit fasting hypoglycemia rather than hyperglycemia

increased circulating insulin level ( J:63878 )

♂ • at 2 months, male mutants exhibit an extreme increase in serum insulin levels (20-fold in fed state; 7-fold in fasted state)

impaired glucose tolerance ( J:63878 )

♂ • at 2 months, fasted male mutants display pronounced glucose intolerance

♂ • surprisingly, glucose intolerance is no longer apparent at 6 months

abnormal insulin clearance ( J:63878 )

• in addition to increased insulin secretion, 11-week-old male mutants show a 75% reduction in the C-peptide:insulin ratio, indicating decreased insulin clearance

insulin resistance ( J:63878 )

♂ • at 2 months, random-fed male mutants are severely resistant to the blood glucose-lowering effects of exogenously administered insulin

abnormal lipid homeostasis ( J:63878 )

decreased circulating free fatty acids level ( J:63878 )

♂ • at 2 months, male mutants show a 40-50% reduction in the levels of serum free fatty acids

decreased circulating triglyceride level ( J:63878 )

♂ • at 2 months, male mutants show a 40-50% reduction in the levels of serum triglycerides

increased bile salt level ( J:92861 )

• mutant gallbladders show a notable increase in bile volume

liver/biliary system

enlarged gallbladder ( J:63878 )

• at 6- to 12-months of age, mutant gall bladders appear enlarged

abnormal liver morphology ( J:63878 )

• at 6- to 12-months of age, mutant livers display multiple hyperplastic pale nodules scattered throughout all lobes

• by 12 months, the normal lobular structure is disrupted; hyperplastic nodules consist of highly vacuolated cells that compress the adjacent normal tissue, in the absence of fibrosis

abnormal hepatocyte morphology ( J:63878 )

• at 6 months, mutant hepatocytes exhibit a moderate increase in lipid accumulation; only a few electron-dense glycogen granules are observed

small liver ( J:63878 )

• at 2 months, mutant livers are 40% smaller than those of age- and sex-matched controls; liver size decreases significantly with increasing age

dark liver ( J:63878 )

• at 2 months, mutant livers appear a little darker in color, with areas of focal dysplasia and reduced glycogen storage in the parenchyma; no steatosis is observed

abnormal liver physiology ( J:63878 )

• insulin resistance in liver results in elevated expression of PEPCK, the rate-limiting enzyme for gluconeogenesis, and reduced expression of glucokinase and liver pyruvate kinase, two enzymes critical for glucose utilization

• the mutant liver appears to be chronically geared toward glucose production; early insulin signaling events, such as IRS-1 and IRS-2 phosphorylation, are lost

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:63878 , J:92861 )

• at 6 months, increased pancreatic insulin content is associated with a 6-fold increase in pancreatic beta cell mass (J:63878)

• at 6 months, mutant mice show a ~4-fold increase in pancreatic beta cell mass, as a compensatory response to insulin resistance (J:92861)

pancreatic islet hyperplasia ( J:92861 )

• at 6 months, mutant mice show an adaptive islet hyperplastic response to insulin resistance

enlarged gallbladder ( J:63878 )

• at 6- to 12-months of age, mutant gall bladders appear enlarged

increased insulin secretion ( J:63878 )

♀ • at 6 months, female mutants show a have 5- to 6-fold increase in pancreatic insulin content measured in acid-ethanol extracts

cellular

increased mitochondrial size ( J:63878 )

• at 6 months, mutant hepatocytes exhibit giant mitochondria

growth/size/body

enlarged gallbladder ( J:63878 )

• at 6- to 12-months of age, mutant gall bladders appear enlarged

postnatal growth retardation ( J:63878 )

• newborn mutant mice appear normal, nurse successfully, and survive well upon weaning but display a mild growth deficit postweaning

• this moderate growth deficit appears to result from defects in the growth hormone-IGF axis (unpublished data)

Genotype
MGI:3812018

cn112

• Allelic Composition: Zbtb20^tm1Wpjz/Zbtb20^tm1Wpjz; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:140053 )

N • mice exhibit normal liver appearance and size

Genotype
MGI:4359908

cn113

• Allelic Composition: Ghr^tm1.1Masp/Ghr^tm1.1Masp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * DBA

Decreased bone density in Ghr^tm1.1Masp/Ghr^tm1.1Masp Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

homeostasis/metabolism

increased circulating insulin level ( J:152627 )

• 2 to 3 times

decreased circulating insulin-like growth factor I level ( J:152627 )

• 95%

increased circulating growth hormone level ( J:152627 )

• 4-fold

increased circulating free fatty acids level ( J:152627 )

• 30%

decreased circulating triglyceride level ( J:152627 )

impaired glucose tolerance ( J:152627 )

decreased liver triglyceride level ( J:152627 )

• triglyceride secretion from the liver is impaired compared to in wild-type mice

liver/biliary system

increased liver weight ( J:152627 )

decreased liver triglyceride level ( J:152627 )

• triglyceride secretion from the liver is impaired compared to in wild-type mice

hepatic steatosis ( J:152627 )

renal/urinary system

decreased kidney weight ( J:152627 )

skeleton

decreased bone mineral density ( J:152627 )

growth/size/body

increased liver weight ( J:152627 )

Genotype
MGI:6295913

cn114

• Allelic Composition: Cdk5rap3^{tm1c(EUCOMM)Hmgu}/Cdk5rap3^{tm1c(EUCOMM)Hmgu}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6N * DBA

mortality/aging

mortality/aging ( J:272566 )

N • mice survive to adulthood

liver/biliary system

liver/biliary system phenotype ( J:272566 )

N • mice exhibit normal liver histology

Genotype
MGI:3029211

cn115

• Allelic Composition: Pck1^tm1.1Mgn/Pck1^tm1.1Mgn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac

homeostasis/metabolism

increased circulating free fatty acids level ( J:63929 )

increased circulating triglyceride level ( J:63929 )

decreased liver glycogen level ( J:63929 )

• hepatic glycogen content was decreased at birth, reduced in older mutant animals and was depleted after a 24 hour fast

increased liver triglyceride level ( J:63929 )

• hepatic triglyceride levels were increased by 94% after a 24 hour fast

liver/biliary system

enlarged liver ( J:63929 )

• after a 24 hour fast, the liver mass was increased by 71% over controls

increased liver weight ( J:63929 )

• liver weight was increased by 18%

decreased liver glycogen level ( J:63929 )

• hepatic glycogen content was decreased at birth, reduced in older mutant animals and was depleted after a 24 hour fast

increased liver triglyceride level ( J:63929 )

• hepatic triglyceride levels were increased by 94% after a 24 hour fast

pale liver ( J:63929 )

growth/size/body

enlarged liver ( J:63929 )

• after a 24 hour fast, the liver mass was increased by 71% over controls

increased liver weight ( J:63929 )

• liver weight was increased by 18%

Genotype
MGI:3578114

cn116

• Allelic Composition: Abca1^tm1Jp/Abca1⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * B6.Cg-Tg(Alb-cre)21Mgn/J

homeostasis/metabolism

abnormal circulating phospholipid level ( J:98093 )

• decreased (70-90%) phospholipid levels

abnormal cholesterol homeostasis ( J:98093 )

• slightly higher catabolism of HDL apoA-I from wildtype mice or human lipid-free ApoA-I than in wildtype, due to an increase in the catabolism of apoA-I by the kidney, with no change in liver catabolism

decreased circulating cholesterol level ( J:98093 )

• decreased levels of total plasma cholesterol, free cholesterol, and esterified cholesterol

decreased circulating HDL cholesterol level ( J:98093 )

Genotype
MGI:3578113

cn117

• Allelic Composition: Abca1^tm1Jp/Abca1^tm1Jp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * B6.Cg-Tg(Alb-cre)21Mgn/J

homeostasis/metabolism

abnormal circulating phospholipid level ( J:98093 )

• 70-90% reduction in plasma phospholipid level

increased circulating triglyceride level ( J:98093 )

abnormal cholesterol homeostasis ( J:98093 )

• 2-fold higher catabolism of HDL apoA-I from wildtype mice or human lipid-free ApoA-I than in wildtype, due to a 2-fold increase in the catabolism of apoA-I by the kidney, with no change in liver catabolism

decreased circulating cholesterol level ( J:98093 )

• total plasma cholesterol levels were 80% lower than in wildtype

• 70-90% reduction in plasma free cholesterol and esterified cholesterol

decreased circulating HDL cholesterol level ( J:98093 )

• 80% lower than in wildtype

decreased circulating LDL cholesterol level ( J:98093 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Tangier disease		DOID:1388	OMIM:205400	J:98093

Genotype
MGI:3832404

cn118

• Allelic Composition: Gt(ROSA)26Sor^{tm3(HIF1A*)Kael}/Gt(ROSA)26Sor^{tm4(HIF2A*)Kael}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA

mortality/aging

premature death ( J:144666 )

• mice die at 6 to 8 weeks of age

liver/biliary system

increased hepatocyte proliferation ( J:144666 )

abnormal liver morphology ( J:144666 )

• at 6 weeks, the liver is friable and stippled with irregular yellow spots on a reddish black background unlike in wild-type mice

• hepatic vascularity is increased compared to in wild-type mice

increased liver weight ( J:144666 )

• at 6 weeks of age

hepatic steatosis ( J:144666 )

• in a mixed micro- and macrovesicular steatotic pattern

hematopoietic system

increased hematocrit ( J:144666 )

reticulocytosis ( J:144666 )

cardiovascular system

abnormal blood vessel morphology ( J:144666 )

• hepatic vascularity is increased compared to in wild-type mice

growth/size/body

growth/size/body region phenotype ( J:144666 )

N • unlike in Vhl^tm1Jae/Vhl^tm1Jae Tg(Alb-cre)21Mgn mice, body weight is normal

increased liver weight ( J:144666 )

• at 6 weeks of age

integument

reddish skin ( J:144666 )

• of paws and unfurred skin by 4 to 6 weeks of age

cellular

increased hepatocyte proliferation ( J:144666 )

Genotype
MGI:3832402

cn119

• Allelic Composition: Gt(ROSA)26Sor^{tm3(HIF1A*)Kael}/Gt(ROSA)26Sor⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA

mortality/aging

mortality/aging ( J:144666 )

N • mice exhibit a normal life span

liver/biliary system

abnormal hepatocyte morphology ( J:144666 )

• hepatocytes exhibit fine vacuolization unlike in wild-type mice but are otherwise normal

microvesicular hepatic steatosis ( J:144666 )

• moderate and in a microvesicular pattern

Genotype
MGI:3832403

cn120

• Allelic Composition: Gt(ROSA)26Sor^{tm4(HIF2A*)Kael}/Gt(ROSA)26Sor⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA

mortality/aging

premature death ( J:144666 )

• mice die at 6 to 8 weeks of age

liver/biliary system

increased hepatocyte proliferation ( J:144666 )

abnormal liver morphology ( J:144666 )

• at 6 weeks, the liver is friable and stippled with irregular yellow spots on a reddish black background unlike in wild-type mice

• livers exhibit vascular lesions observed in Vhl^tm1Jae/Vhl^tm1Jae Tg(Alb-cre)21Mgn mice with minimal evidence of vacuolization

• hepatic vascularity is increased compared to in wild-type mice

increased liver weight ( J:144666 )

• at 6 weeks of age

hepatic steatosis ( J:144666 )

• minimal

hematopoietic system

increased hematocrit ( J:144666 )

reticulocytosis ( J:144666 )

cardiovascular system

abnormal blood vessel morphology ( J:144666 )

• hepatic vascularity is increased compared to in wild-type mice

growth/size/body

growth/size/body region phenotype ( J:144666 )

N • unlike in Vhl^tm1Jae/Vhl^tm1Jae Tg(Alb-cre)21Mgn mice, body weight is normal

increased liver weight ( J:144666 )

• at 6 weeks of age

integument

reddish skin ( J:144666 )

• of paws and unfurred skin by 4 to 6 weeks of age

cellular

increased hepatocyte proliferation ( J:144666 )

Genotype
MGI:5792902

cn121

• Allelic Composition: Hjv^tm1Kpan/Hjv^tm1Kpan; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

homeostasis/metabolism

increased circulating ferritin level ( J:231428 )

♂ • significantly increased serum ferritin levels at 10 weeks of age

decreased circulating unsaturated transferrin level ( J:231428 )

♂ • significantly elevated transferrin saturation at 10 weeks of age

abnormal iron homeostasis ( J:231428 )

♂ • 13.1-fold decrease in hepcidin mRNA expression in liver

♂ • 2.4-fold increase in hepatic BMP6 mRNA levels

♂ • marked up-regulation of ferroportin in the duodenum

♂ • however, duodenal BMP6 mRNA expression is largely normal

decreased spleen iron level ( J:231428 )

♂ • 2.4-fold reduction of nonheme iron levels in spleen at 10 weeks of age

♂ • splenic macrophages are iron-deficient

increased circulating iron level ( J:231428 )

♂ • significantly increased serum iron levels at 10 weeks of age

increased liver iron level ( J:231428 )

♂ • 12.9-fold increase of nonheme iron levels in liver at 10 weeks of age, as determined by ferrozine assay

hemochromatosis ( J:231428 )

♂ • deposits of nonheme iron in parenchymal cells of the liver, pancreas, and heart at 10 weeks of age

hematopoietic system

abnormal macrophage morphology ( J:231428 )

♂ • splenic macrophages are iron-deficient

decreased spleen iron level ( J:231428 )

♂ • 2.4-fold reduction of nonheme iron levels in spleen at 10 weeks of age

♂ • splenic macrophages are iron-deficient

liver/biliary system

increased liver iron level ( J:231428 )

♂ • 12.9-fold increase of nonheme iron levels in liver at 10 weeks of age, as determined by ferrozine assay

immune system

abnormal macrophage morphology ( J:231428 )

♂ • splenic macrophages are iron-deficient

decreased spleen iron level ( J:231428 )

♂ • 2.4-fold reduction of nonheme iron levels in spleen at 10 weeks of age

♂ • splenic macrophages are iron-deficient

Genotype
MGI:5691397

cn122

• Allelic Composition: Lamp2^tm1Amcu/Y; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J

growth/size/body

decreased body weight ( J:215605 )

♂ • mutant males exhibit a significantly lower body weight than control males up to 3.5 months of age

♂ • however, this difference is not visible after 4 months of age

weight loss ( J:215605 )

♂ • after 24 or 48 hr starvation, 4-month-old males display a greater % of body weight loss than control mice

increased susceptibility to weight gain ( J:215605 )

♂ • despite a higher EE, mutant mice gain more weight on a HFD and show increased fat mass and liver and perigonadal WAT weight gains than control mice

enlarged liver ( J:215605 )

♂ • mutant mice display enlarged livers

♂ • after 16 weeks on a high-fat diet (HFD; 60% calories from fat), mutant mice exhibit significantly larger livers than control mice

increased liver weight ( J:215605 )

♂ • mutant mice exhibit an increased liver weight relative to body weight

behavior/neurological

enhanced behavioral response to xenobiotic ( J:215605 )

♂ • time for recovery of the righting reflex after zoxazolamine-induced paralysis is significantly increased relative to controls, indicating decreased liver function

decreased locomotor activity ( J:215605 )

♂ • on a regular chow diet, mutant mice exhibit reduced physical activity relative to control mice

homeostasis/metabolism

abnormal autophagy ( J:215605 )

♂ • mice are unable to internalize and degrade select proteins by chaperone-mediated autophagy (CMA)

♂ • in vivo blockage of lysosomal proteolysis by i.p. injection of leupeptin revealed that GAPDH (a known CMA substrate) is no longer degraded in mutant liver lysosomes

♂ • in contrast, lysosomal delivery and degradation of cytosolic proteins such as cyclophillin (a non-CMA substrate) is normal

increased circulating alanine transaminase level ( J:215605 )

♂ • serum ALT levels are significantly increased, indicating hepatocyte damage

♂ • after 16 weeks on a HFD, mice exhibit significantly greater serum ALT levels than control mice

increased energy expenditure ( J:215605 )

♂ • on a regular chow diet, mutant mice show significantly higher energy expenditure (EE) than control mice throughout a 24 hr cycle; however, no difference in food intake (meal number and size) is observed

♂ • a HFD has a significantly smaller impact on lowering the EE in mutant mice relative to control mice

♂ • after a 24 hr starvation, mutant mice exhibit a significantly higher EE than control mice during the day cycle

increased carbon dioxide production ( J:215605 )

♂ • fed mutant mice exhibit higher average values of CO2 production than control mice

increased oxygen consumption ( J:215605 )

♂ • fed mutant mice exhibit higher average values of O2 consumption than control mice

increased respiratory quotient ( J:215605 )

♂ • on a regular chow diet, mutant mice exhibit higher respiratory exchange ratio (RER) values than control mice during the 24 hr cycle

♂ • mutant RER values remain higher than in controls during the first 6 hr of a 24 hr starvation period

abnormal glucose homeostasis ( J:215605 )

♂ • mutant livers exhibit higher lactate content and specific activity of glycolytic enzymes (GAPDH and PK), suggesting enhanced glycolysis

♂ • in culture, primary hepatocytes from mutant mice show significantly higher basal glycolytic rates and maximal glycolytic capacity and higher levels of glycolytic enzymes relative to control hepatocytes; basal and maximal glycolytic capacity remains significantly higher than in controls even 24 hr after removal of serum from the culture media

♂ • after a 24 hr starvation, levels of different glycolytic enzymes in mutant livers remain higher than in control livers

decreased fasting circulating glucose level ( J:215605 )

♂ • after a 8 hr starvation (overnight fasting), mutant mice show a significant drop in blood glucose levels relative to control mice

♂ • reduced blood glucose levels in response to short- and long-term fasting are noted even when mutant mice are fed a HFD

♂ • lower blood glucose observed during starvation are not due to increased circulating insulin levels

improved glucose tolerance ( J:215605 )

♂ • mutant mice display improved glucose tolerance even when placed on a HFD

♂ • lower blood glucose observed during the glucose tolerance test are not due to increased circulating insulin levels

decreased liver glycogen level ( J:215605 )

♂ • biochemical analysis and PAS staining revealed a significant reduction of glycogen content in mutant livers

decreased hepatic glucose production ( J:215605 )

♂ • following injection of a pyruvate bolus (converted into glucose in liver), overnight fasted mutant mice show a significantly smaller increase in blood glucose than controls, suggesting reduced hepatic gluconeogenesis

abnormal lipid homeostasis ( J:215605 )

♂ • mutant mice show a significant reduction in starvation-induced lysosomal degradation of liver enzymes related to lipid metabolism

♂ • lysosomal degradation of some enzymes is also reduced even under fed conditions; accordingly, levels of many lipid metabolic enzymes are increased in mutant liver cytosolic fractions

♂ • in culture, primary hepatocytes from mutant mice show increased content of enzymes involved in lipid metabolism and reduced lysosomal degradation of these enzymes

♂ • although basal oxygen consumption rates are normal, mutant hepatocytes exhibit significantly reduced maximal mitochondrial respiratory capacity, fail to increase mitochondrial respiration in response to a lipogenic challenge and show lower rates of beta-oxidation in these conditions

♂ • the VLDL secretion rate is significantly reduced in mutant livers

increased liver triglyceride level ( J:215605 )

♂ • after two i.p. injections of isoproterenol to induce peripheral lipolysis, mutant livers show a ~5-fold increase in TG content relative to control livers

abnormal enzyme/coenzyme activity ( J:215605 )

♂ • mutant mice exhibit lower basal levels of glycogen synthetase (GS)

♂ • a higher percentage of GS is in an inactive phosphorylated state (pGS)

♂ • however, GS is still efficiently activated, even at higher levels than in control mice, following stimulation of hepatic glycogenesis by insulin injection in overnight starved mice

liver/biliary system

enlarged liver ( J:215605 )

♂ • mutant mice display enlarged livers

♂ • after 16 weeks on a high-fat diet (HFD; 60% calories from fat), mutant mice exhibit significantly larger livers than control mice

increased liver weight ( J:215605 )

♂ • mutant mice exhibit an increased liver weight relative to body weight

decreased liver glycogen level ( J:215605 )

♂ • biochemical analysis and PAS staining revealed a significant reduction of glycogen content in mutant livers

increased liver triglyceride level ( J:215605 )

♂ • after two i.p. injections of isoproterenol to induce peripheral lipolysis, mutant livers show a ~5-fold increase in TG content relative to control livers

hepatic steatosis ( J:215605 )

♂ • mutant hepatocytes contain an increased number and size of cytosolic lipid droplets (LDs), which become even more evident after starvation

♂ • in the fed state, the major lipid species that accumulate in mutant livers are cholesterol esther and triacylglycerides (TG)

♂ • after 24 hr of starvation, mutant livers also accumulate TG precursors, such as free fatty acids (FFAs) and diacylglycerol (DAG)

♂ • after two i.p. injections of isoproterenol to induce peripheral lipolysis, mutant livers display more pronounced LD accumulation than control livers, with a ~5-fold increase in TG content, whereas cholesterol content remains unchanged

♂ • after 16 weeks on a HFD, mutant livers exhibit more pronounced LD accumulation than control livers

pale liver ( J:215605 )

♂ • mutant mice display discolored livers

♂ • after 16 weeks on a HFD, mutant mice exhibit significantly paler livers than control mice

abnormal liver physiology ( J:215605 )

♂ • mutant livers exhibit a switch from carbohydrate synthesis and storage to carbohydrate hydrolysis and utilization

increased hepatocyte apoptosis ( J:215605 )

♂ • liver apoptosis is significantly increased, as shown by TUNEL analysis

decreased liver function ( J:215605 )

♂ • significant decline in liver function as early as 4 months of age, as shown by the increased clearance time of zoxazolamine (a muscle relaxant metabolized by the liver), in a zoxazolamine-induced paralysis time assay

adipose tissue

decreased brown fat cell lipid droplet size ( J:215605 )

♂ • after a 24 hr starvation, mutant mice show smaller adipocyte LDs in interscapular brown adipose tissue (BAT) than control mice

decreased white fat cell lipid droplet size ( J:215605 )

♂ • after a 24 hr starvation, mutant mice show smaller adipocyte LDs in perigonadal WAT than control mice

decreased gonadal fat pad weight ( J:215605 )

♂ • after a 24 hr starvation, mutant mice show reduced perigonadal white adipose tissue (WAT) weight than control mice

decreased percent body fat/body weight ( J:215605 )

♂ • fed mutants exhibit lower total-body fat mass (as a percent of body weight) than control mice; this is further accentuated after a 24 hr starvation

cellular

cellular phenotype ( J:215605 )

♂N • liver lysosomes show no differences in their content of mature hydrolases (e.g. cathepsin D), enzymatic activities (e.g. total liver and lysosomal beta-hexosaminidase activities), or stability of their membranes relative to control lysosomes

♂N • steady state levels of integral autophagosome components and autophagy receptors are normal in mutant livers

♂N • most autophagic vacuoles in mutant livers are autophagolysosomes, and the autophagosome/autophagolysosome ratio is similar to that in control mice

abnormal autophagy ( J:215605 )

♂ • mice are unable to internalize and degrade select proteins by chaperone-mediated autophagy (CMA)

♂ • in vivo blockage of lysosomal proteolysis by i.p. injection of leupeptin revealed that GAPDH (a known CMA substrate) is no longer degraded in mutant liver lysosomes

♂ • in contrast, lysosomal delivery and degradation of cytosolic proteins such as cyclophillin (a non-CMA substrate) is normal

increased hepatocyte apoptosis ( J:215605 )

♂ • liver apoptosis is significantly increased, as shown by TUNEL analysis

increased cellular glucose import ( J:215605 )

♂ • mutant livers display enhanced glucose uptake but reduced usage of glucose for glycogen synthesis

Genotype
MGI:6791347

cn123

• Allelic Composition: Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * C57BL/6NTac

mortality/aging

mortality/aging ( J:234643 )

N • mice are born in the expected Mendelian ratio and survive to adulthood, unlike Mad2l1bp^tm1.2Itl homozygotes

homeostasis/metabolism

hyperglycemia ( J:234643 )

• at 2 months of age, mice show hyperglycemia in the fed state

• surprisingly, blood glucose levels become normal by 6 months of age

• adeno-associated virus (AAV)-mediated expression of MAD2L1BP (but not of GFP) in the liver rescues the hyperglycemia phenotype

increased circulating insulin level ( J:234643 )

• at 2 months of age, mice show hyperinsulinemia in the fed state that is less severe than that in Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

increased circulating triglyceride level ( J:234643 )

• at 2 months of age, serum triglyceride levels are moderately increased

impaired glucose tolerance ( J:234643 )

• at 2 months of age, male mice develop glucose intolerance that is less severe than that in Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

• AAV-mediated expression of MAD2L1BP (but not of GFP) in the liver rescues the glucose intolerance phenotype

decreased liver glycogen level ( J:234643 )

• at E18.5, liver glycogen levels are decreased but to a much lesser extent than in Mad2l1bp^tm1.2Itl homozygotes, thus enabling survival

• at 2 months of age, liver glycogen levels are reduced but to a lesser extent than in Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

• however, no liver developmental defects are noted at E18.5 or at 2 months of age

insulin resistance ( J:234643 )

• at 2 months of age, male mice develop insulin intolerance that is less severe than that in Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

• AAV-mediated expression of MAD2L1BP (but not of GFP) in the liver rescues the insulin intolerance phenotype

decreased liver triglyceride level ( J:234643 )

• at 2 months of age, hepatic triglyceride levels are decreased by about 50%

abnormal enzyme/coenzyme activity ( J:234643 )

• insulin treatment fails to stimulate glycogen synthase activity (GS) in hepatocytes, unlike in wild-type hepatocytes

liver/biliary system

decreased liver glycogen level ( J:234643 )

• at E18.5, liver glycogen levels are decreased but to a much lesser extent than in Mad2l1bp^tm1.2Itl homozygotes, thus enabling survival

• at 2 months of age, liver glycogen levels are reduced but to a lesser extent than in Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

• however, no liver developmental defects are noted at E18.5 or at 2 months of age

decreased liver triglyceride level ( J:234643 )

• at 2 months of age, hepatic triglyceride levels are decreased by about 50%

abnormal liver physiology ( J:234643 )

• insulin receptor (IR) autophosphorylation and activating phosphorylation of AKT (pT308) are significantly reduced whereas inhibitory phosphorylation of GSK3 (pS9) is modestly reduced in whole-liver lysates from insulin-treated mice

• AAV-mediated expression of MAD2L1BP (but not of GFP) in the liver rescues the insulin signaling defects

abnormal hepatocyte physiology ( J:234643 )

• insulin-dependent glycogen synthase (GS) activation is abolished in hepatocytes

• freshly isolated primary hepatocytes display weakened and delayed IR autophosphorylation and AKT pT308 at multiple time points and over a wide range of insulin concentrations

cellular

aneuploidy ( J:234643 )

• only 10% (1 out of 10) live hepatocytes is aneuploid relative to none (0 of 15) wild-type hepatocytes

• AAV-mediated expression of MAD2L1BP does not eliminate aneuploidy: 5% (2 of 39) hepatocytes are aneuploid vs only 2.5% (1 of 40) hepatocytes in the AAV-GFP control group

abnormal endocytosis ( J:234643 )

• hepatocytes show defective insulin endocytosis as a result of a reduced level of functional IR at the plasma membrane, due to premature internalization of IR prior to insulin stimulation

Genotype
MGI:7611650

cn124

• Allelic Composition: Tor1a^tm3.1Wtd/Tor1a^tm3.1Wtd; Tor1aip1^tm1.1Wtd/Tor1aip1⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA

liver/biliary system

hepatic steatosis ( J:345574 )

• grossly white livers

Genotype
MGI:5461227

cn125

• Allelic Composition: Il7^tm2.1Iku/Il7^tm2.1Iku; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA

immune system

immune system phenotype ( J:190615 )

N • mice exhibit normal numbers of hepatic NK, dendritic and B cells

N • development and maintenance of NK T and T cells in the lymphoid organs is normal

abnormal B cell differentiation ( J:190615 )

• impaired fetal and neonatal B cell development

decreased lymphocyte cell number ( J:190615 )

• intrahepatic lymphocytes

decreased B cell number ( J:190615 )

• in fetal and neonatal liver samples

decreased T cell number ( J:190615 )

• in the liver

decreased double-negative T cell number ( J:190615 )

• in the liver

decreased NK T cell number ( J:190615 )

• of NK T and invariant NK T (5-fold) cells in the liver

• however, the number of invariant NK T cells in the thymus and spleen is normal

abnormal NK T cell physiology ( J:190615 )

• impaired hepatic invariant NK T cell maintenance

• however, development and maintenance of NK T and T cells in the lymphoid organs is normal

hematopoietic system

hematopoietic system phenotype ( J:190615 )

N • mice exhibit normal numbers of hematopoietic progenitors

abnormal B cell differentiation ( J:190615 )

• impaired fetal and neonatal B cell development

decreased lymphocyte cell number ( J:190615 )

• intrahepatic lymphocytes

decreased B cell number ( J:190615 )

• in fetal and neonatal liver samples

decreased T cell number ( J:190615 )

• in the liver

decreased double-negative T cell number ( J:190615 )

• in the liver

decreased NK T cell number ( J:190615 )

• of NK T and invariant NK T (5-fold) cells in the liver

• however, the number of invariant NK T cells in the thymus and spleen is normal

abnormal NK T cell physiology ( J:190615 )

• impaired hepatic invariant NK T cell maintenance

• however, development and maintenance of NK T and T cells in the lymphoid organs is normal

Genotype
MGI:7611647

cn126

• Allelic Composition: Tor1a^tm3.1Wtd/Tor1a^tm3.1Wtd; Tor1aip1^tm1.1Wtd/Tor1aip1^tm1.1Wtd; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA

liver/biliary system

abnormal hepatocyte morphology ( J:345574 )

• decrease in the number of nuclei containing 2 or more lipid droplets compared to mutant mice wild-type for Tor1a, 7 +/- 3% compared to 64 +/- 5%

hepatic steatosis ( J:345574 )

• grossly white livers

abnormal liver physiology ( J:345574 )

• decreased triglyceride, apoB100, and apoB48 secretion rates

Genotype
MGI:7611649

cn127

• Allelic Composition: Tor1a^tm3.1Wtd/Tor1a^tm3.1Wtd; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA

liver/biliary system

hepatic steatosis ( J:345574 )

• grossly white livers

Genotype
MGI:4462847

cn128

• Allelic Composition: Gys2^tm1.1Pro/Gys2^tm1.1Pro; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA

Decreased glycogen liver content in Gys2^tm1.1Pro/Gys2^tm1.1Pro Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

homeostasis/metabolism

impaired exercise endurance ( J:162043 )

• fed mice exhibit reduced exercise capacity compared with control Gys2^tm1.1Pro homozygotes

abnormal circulating ketone body level ( J:162043 )

• during a fast, mice exhibit a more acute increase in ketone bodies than in similarly treated control Gys2^tm1.1Pro homozygotes

abnormal glucose homeostasis ( J:162043 )

decreased circulating glucose level ( J:162043 )

• in fed and fasted states, mice exhibit reduced circulating glucose levels compared with similarly treated control Gys2^tm1.1Pro homozygotes

• mice enter a fasted state quicker than similarly treated control Gys2^tm1.1Pro homozygotes

decreased circulating insulin level ( J:162043 )

• under fed condition

abnormal gluconeogenesis ( J:162043 )

• mice exhibit enhanced gluconeogenesis compared with control Gys2^tm1.1Pro homozygotes

impaired glucose tolerance ( J:162043 )

decreased glycogen catabolism rate ( J:162043 )

decreased glycogen level ( J:162043 )

• glycogen liver content is reduced 94% compared to in control Gys2^tm1.1Pro homozygotes

• exercised mice exhibit a greater decrease in muscle glycogen levels compared with control Gys2^tm1.1Pro homozygotes

• however, glycogen content in the skeletal muscle and kidney is normal

abnormal triglyceride level ( J:162043 )

• fasting mice fail to exhibit a change in triglyceride levels unlike fasted control Gys2^tm1.1Pro homozygotes

increased liver triglyceride level ( J:162043 )

• at 7 and 15 months

cardiovascular system

decreased heart weight ( J:162043 )

decreased cardiac muscle cell glucose uptake ( J:162043 )

• heart glucose uptake is lower than in control Gys2^tm1.1Pro homozygotes

decreased systemic arterial diastolic blood pressure ( J:162043 )

liver/biliary system

increased liver triglyceride level ( J:162043 )

• at 7 and 15 months

decreased liver weight ( J:162043 )

muscle

decreased cardiac muscle cell glucose uptake ( J:162043 )

• heart glucose uptake is lower than in control Gys2^tm1.1Pro homozygotes

behavior/neurological

impaired exercise endurance ( J:162043 )

• fed mice exhibit reduced exercise capacity compared with control Gys2^tm1.1Pro homozygotes

cellular

decreased cardiac muscle cell glucose uptake ( J:162043 )

• heart glucose uptake is lower than in control Gys2^tm1.1Pro homozygotes

Genotype
MGI:7611653

cn129

• Allelic Composition: Tor1a^tm3.1Wtd/Tor1a⁺; Tor1aip1^tm1.1Wtd/Tor1aip1^tm1.1Wtd; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * DBA

liver/biliary system

abnormal hepatocyte morphology ( J:345574 )

• decrease in the number of nuclei containing 2 or more lipid droplets compared to mutant mice wild-type for Tor1a, 33 +/- 7% compared to 64 +/- 5%

hepatic steatosis ( J:345574 )

• grossly white livers

Genotype
MGI:6719082

cn130

• Allelic Composition: Tjp1^tm1.1Whun/Tjp1^tm1.1Whun; Tjp2^tm2Whun/Tjp2^tm2Whun; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2

mortality/aging

premature death ( J:306936 )

• 70-80% die by 4 weeks and all die by 6 weeks of age

postnatal lethality, incomplete penetrance ( J:306936 )

• mice start to die around 2 weeks of age

growth/size/body

increased liver weight ( J:306936 )

• mean liver weight-to-body weight ratio is increased

liver/biliary system

abnormal hepatic duct morphology ( J:306936 )

• marker analysis shows no, or rare, bile ducts in the periportal zone of the liver

abnormal liver morphology ( J:306936 )

• liver is yellowish

• targeting of tight junctions and apical molecules is disrupted in the liver

• marker analysis indicates that liver zonation is perturbed

• however, no liver inflammation or fibrosis are seen

abnormal liver sinusoid morphology ( J:306936 )

• the lumina of the sinusoidal vessels are not clear

• marker analysis shows that sinusoidal vessels in the liver are injured

increased liver weight ( J:306936 )

• mean liver weight-to-body weight ratio is increased

abnormal hepatic cord morphology ( J:306936 )

• the hepatic cords are not well-organized in the liver

abnormal bile canaliculus morphology ( J:306936 )

• normal bile canaliculi are hardly seen

abnormal hepatocyte morphology ( J:306936 )

• individual hepatocytes appear slightly swollen with vacuole-like structures inside

• hepatocytes exhibit ectopic luminal structures around their basolateral domains

• hepatocyte cellular polarity is disrupted, with an unclear distinction between the apical and basolateral plasma membrane domains

small liver ( J:306936 )

abnormal liver physiology ( J:306936 )

• mice show disruption of the hepatic barrier

• bile transport into bile canaliculi is diminished

increased hepatocyte proliferation ( J:306936 )

• mice show an increase in Ki-67+ hepatocytes, indicating increased hepatocyte proliferation

homeostasis/metabolism

increased circulating bilirubin level ( J:306936 )

• mice show increased levels of total bilirubin and direct bilirubin

increased circulating LDL cholesterol level ( J:306936 )

increased circulating alanine transaminase level ( J:306936 )

increased circulating alkaline phosphatase level ( J:306936 )

• mice show increased levels of alkaline phosphatase

• however, gamma-glutamyl transferase levels are normal

increased circulating aspartate transaminase level ( J:306936 )

increased bile salt level ( J:306936 )

• mice show increased levels of bile acids

cardiovascular system

abnormal liver sinusoid morphology ( J:306936 )

• the lumina of the sinusoidal vessels are not clear

• marker analysis shows that sinusoidal vessels in the liver are injured

cellular

increased hepatocyte proliferation ( J:306936 )

• mice show an increase in Ki-67+ hepatocytes, indicating increased hepatocyte proliferation

endocrine/exocrine glands

abnormal hepatic duct morphology ( J:306936 )

• marker analysis shows no, or rare, bile ducts in the periportal zone of the liver

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
progressive familial intrahepatic cholestasis 4		DOID:0070224	OMIM:615878	J:306936

Genotype
MGI:6719086

cn131

• Allelic Composition: Tjp2^tm2Whun/Tjp2^tm2Whun; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac * DBA/2

homeostasis/metabolism

increased circulating LDL cholesterol level ( J:306936 )

increased circulating alanine transaminase level ( J:306936 )

increased circulating aspartate transaminase level ( J:306936 )

liver/biliary system

liver/biliary system phenotype ( J:306936 )

N • mice show normal total and direct bilirubin levels, bile acids, and alkaline phosphatase levels, and normal livers

Genotype
MGI:4430548

cn132

• Allelic Composition: Sav1^tm1.1Rjo/Sav1^tm1.1Rjo; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CD-1 * DBA * SJL

liver/biliary system

increased hepatocyte proliferation ( J:156531 )

• increased BrdU incorporation

increased liver weight ( J:156531 )

• 10% increase in liver size by 4months of age

increased hepatocellular carcinoma incidence ( J:156531 )

• mice at 13-14 months of age develop large liver tumors that are hepatocellular carcinoma and cholangiocarcinoma like

neoplasm

increased carcinoma incidence ( J:156531 )

• mice at 13-14 months of age develop large liver tumors that are hepatocellular carcinoma and cholangiocarcinoma like

increased hepatocellular carcinoma incidence ( J:156531 )

• mice at 13-14 months of age develop large liver tumors that are hepatocellular carcinoma and cholangiocarcinoma like

cellular

increased hepatocyte proliferation ( J:156531 )

• increased BrdU incorporation

growth/size/body

increased liver weight ( J:156531 )

• 10% increase in liver size by 4months of age

Genotype
MGI:4430567

cn133

• Allelic Composition: Stk3^tm1.1Rjo/Stk3^tm1.1Rjo; Stk4^tm1.1Rjo/Stk4^tm1.1Rjo; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CD-1 * DBA * SJL

liver/biliary system

increased hepatocyte apoptosis ( J:156531 )

• modest increases in cell death of hepatocytes

increased hepatocyte proliferation ( J:156531 )

• increased proliferation index at 3 months of age as measure by elevated levels of BrdU incorporation

abnormal liver morphology ( J:156531 )

• at 2 months of age, large numbers of small periductal cells are visible that infiltrate the liver parenchyma

• at 3 months of age, small periductal cells surround the hepatic plates

abnormal liver sinusoid morphology ( J:156531 )

• an irregular arrangement of hepatocytes that obscures the normal radiating pattern of liver sinusoids

increased liver weight ( J:156531 )

• a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age

abnormal hepatocyte morphology ( J:156531 )

• hepatocytes exhibit a "clear cell" phenotype

increased liver tumor incidence ( J:156531 )

• tumors are detectable in some mice at 3 months of age and in all mice at 4 months of age

• livers are highly enlarged and have multiple focal tumors visible at 5-6 months of age

• disorganized parenchyma with the majority of the liver exhibiting a dysplastic partially transformed phenotype

increased hepatocellular carcinoma incidence ( J:156531 )

• the histopathology of tumor nodules is consistent with a diagnosis of hepatocellular carcinoma

neoplasm

increased liver tumor incidence ( J:156531 )

• tumors are detectable in some mice at 3 months of age and in all mice at 4 months of age

• livers are highly enlarged and have multiple focal tumors visible at 5-6 months of age

• disorganized parenchyma with the majority of the liver exhibiting a dysplastic partially transformed phenotype

increased hepatocellular carcinoma incidence ( J:156531 )

• the histopathology of tumor nodules is consistent with a diagnosis of hepatocellular carcinoma

cardiovascular system

abnormal liver sinusoid morphology ( J:156531 )

• an irregular arrangement of hepatocytes that obscures the normal radiating pattern of liver sinusoids

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:156531 )

N • despite morphological liver changes, no increase in serum alanine aminotransferase or aspartate aminotransferase levels are detected at 2 months of age

cellular

increased hepatocyte apoptosis ( J:156531 )

• modest increases in cell death of hepatocytes

increased hepatocyte proliferation ( J:156531 )

• increased proliferation index at 3 months of age as measure by elevated levels of BrdU incorporation

growth/size/body

increased liver weight ( J:156531 )

• a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age

Genotype
MGI:5519060

cn134

• Allelic Composition: Gclc^tm1Tdal/Gclc^tm1Tdal; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

mortality/aging

premature death ( J:202376 )

• mice become moribund at 30 days of age and are euthanized

growth/size/body

postnatal growth retardation ( J:202376 )

• although normal at birth, mice become growth retarded after 14 days of age

homeostasis/metabolism

abnormal homeostasis ( J:202376 )

• glutathione levels in the liver are about 37% of normal at 14 days of age

• glutathione levels in plasma are extremely low at 14 days of age

increased circulating alanine transaminase level ( J:202376 )

• plasma levels are dramatically elevated by 28 days of age

increased circulating aspartate transaminase level ( J:202376 )

• plasma levels are dramatically elevated by 28 days of age

liver/biliary system

abnormal liver morphology ( J:202376 )

• vacuolated hepatocytes are diffusely present at 21 days of age

• both macrovesicular and microvesicular vacuoles are found

• vacuoles contain neutral lipid

• scattered instances of single cell death

• increased number of binucleate hepatocytes

hepatic steatosis ( J:202376 )

• increasing steatosis from 21 days (26%) to 28 days of age (69%)

cellular

abnormal endoplasmic reticulum morphology ( J:202376 )

• loss of lamellar rough endoplasmic reticulum in hepatocytes by 28 days of age

• replaced by small vesicles lacking ribosomes

abnormal mitochondrial morphology ( J:202376 )

• 20% of mitochondria are morphologically abnormal in hepatocytes at 21 days of age

decreased mitochondrial number ( J:202376 )

• mitochondrion number in hepatocytes is 42% of control numbers at 14 days and 16% at 28 days of age

abnormal mitochondrial physiology ( J:202376 )

• mitochondrial respiratory control ratios in hepatocytes are reduced at 21 days

• decreased oxygen consumption at state 3 respiration

• poorly coupled at 25 and 28 days

• decreased membrane potentials

• reduced liver ATP

• increased lipid peroxidation

Genotype
MGI:5305778

cn135

• Allelic Composition: Gak^tm2Legr/Gak^tm2Legr; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

mortality/aging

postnatal lethality, complete penetrance ( J:180119 )

• by P5

liver/biliary system

abnormal bile duct morphology ( J:180119 )

• not well organized

abnormal hepatoblast differentiation ( J:180119 )

• hepatoblasts fail to differentiate

abnormal liver morphology ( J:180119 )

• yellowish liver

decreased liver glycogen level ( J:180119 )

• mice fail to accumulate glycogen unlike control mice

jaundice ( J:180119 )

• at P1 or P2

growth/size/body

increased body weight ( J:180119 )

• small during the first 4 days after birth

decreased body size ( J:180119 )

• at P1 or P2

homeostasis/metabolism

decreased liver glycogen level ( J:180119 )

• mice fail to accumulate glycogen unlike control mice

endocrine/exocrine glands

abnormal bile duct morphology ( J:180119 )

• not well organized

Genotype
MGI:3795939

cn136

• Allelic Composition: Hdac3^tm1Swh/Hdac3^tm1.1Swh; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

mortality/aging

mortality/aging ( J:134288 )

N • unlike homozygous null mice, mice with loss of expression in the liver after birth are viable

liver/biliary system

increased hepatocyte proliferation ( J:134288 )

• at 6 - 8 weeks of age, but not at P17, the number of proliferating cells is increased

enlarged liver ( J:134288 )

• by P28 livers are hypertrophic

increased liver weight ( J:134288 )

• ratio of liver weight to body weight is increased to about 25 - 30% compared to about 5% in heterozygous mice

decreased liver glycogen level ( J:134288 )

• dramatic depletion of glycogen in hepatocytes

increased liver triglyceride level ( J:134288 )

• up to a 17-fold increase in triglyceride levels in the liver at P17

abnormal hepatocyte morphology ( J:134288 )

• cells with abnormal cytoplasm are apparent at P17

hepatic steatosis ( J:134288 )

• accumulation of lipid droplets

• elevated triglyceride levels at P17

• treating mice with rapamycin reduces neutral lipid accumulation but does not alter the increase in liver size

pale liver ( J:134288 )

• by P28

homeostasis/metabolism

increased circulating triglyceride level ( J:134288 )

• increases with age

increased circulating alanine transaminase level ( J:134288 )

• by P17

abnormal glucose homeostasis ( J:134288 )

hypoglycemia ( J:134288 )

• present by 6 weeks of age but not at P17

• at 10 weeks of age fasting glucose level is almost 2-fold lower than in control littermates

• however, glucose tolerance is not significantly different from controls

decreased circulating glucagon level ( J:134288 )

• slightly lower at P17

decreased circulating insulin level ( J:134288 )

• dramatic decrease by P28 which persists as mice age

decreased liver glycogen level ( J:134288 )

• dramatic depletion of glycogen in hepatocytes

increased cholesterol level ( J:134288 )

• increases with age

increased circulating cholesterol level ( J:134288 )

• increases with age

increased circulating LDL cholesterol level ( J:134288 )

• increases with age

increased liver triglyceride level ( J:134288 )

• up to a 17-fold increase in triglyceride levels in the liver at P17

growth/size/body

decreased body size ( J:134288 )

• by 4 - 6 weeks of age

enlarged liver ( J:134288 )

• by P28 livers are hypertrophic

increased liver weight ( J:134288 )

• ratio of liver weight to body weight is increased to about 25 - 30% compared to about 5% in heterozygous mice

adipose tissue

decreased total body fat amount ( J:134288 )

• visibly leaner with a substantial reduction in visceral adipose tissue by 6 - 8 weeks of age

cellular

increased hepatocyte proliferation ( J:134288 )

• at 6 - 8 weeks of age, but not at P17, the number of proliferating cells is increased

Genotype
MGI:4439273

cn137

• Allelic Composition: Hs6st1^tm1Wvc/Hs6st1^tm1Wvc; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:158299 )

N • mice do not accumulate plasma triglycerides

Genotype
MGI:4358982

cn138

• Allelic Composition: Abca1^tm1Jp/Abca1^tm1Jp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

homeostasis/metabolism

decreased circulating HDL cholesterol level ( J:107802 )

• HDL levels are reduced by 80%

Genotype
MGI:3603013

cn139

• Allelic Composition: Gck^tm1.1Mgn/Gck^tm1.1Mgn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

homeostasis/metabolism

abnormal glucose homeostasis ( J:51826 )

decreased insulin secretion ( J:51826 )

• secrete 70% less insulin in response to glucose stimulus

increased circulating glucose level ( J:51826 )

• 10% increase in fed blood glucose concentration

increased circulating insulin level ( J:51826 )

• post-absorptive (fed) plasma insulin concentrations twice that of controls

impaired glucose tolerance ( J:51826 )

• glucose turnover and glucose infusion rates during hyperglycemic clamp are reduced

decreased glycogen level ( J:51826 )

• net hepatic glycogen synthesis is reduced by about 90% during hyperglycemic clamp studies

insulin resistance ( J:51826 )

• mild insulin resistance

endocrine/exocrine glands

decreased insulin secretion ( J:51826 )

• secrete 70% less insulin in response to glucose stimulus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young type 2		DOID:0111100	OMIM:125851	J:51826

Genotype
MGI:4438748

cn140

• Allelic Composition: Chrm3^tm2.1Jwe/Chrm3^tm2.1Jwe; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA * FVB/N

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:158245 )

N • mice exhibit largely normal glucose metabolism whether fed a standard or high fat diet

decreased circulating glucose level ( J:158245 )

• slight after 30 minutes in an oral glucose tolerance test in mice fed a standard diet

• slight after 60 minutes in an oral glucose tolerance test in mice fed a high fat diet

growth/size/body

growth/size/body region phenotype ( J:158245 )

N • mice exhibit normal weight and growth whether fed a standard or high fat diet

Genotype
MGI:4358977

cn141

• Allelic Composition: Abca1^tm1Jp/Abca1^tm1Jp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA * SJL

homeostasis/metabolism

decreased circulating HDL cholesterol level ( J:107802 )

• plasma HDL levels are reduced by 90%

Genotype
MGI:6791353

cn142

• Allelic Composition: Bub1b^tm1Jvd/Bub1b^tm1Jvd; Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB

mortality/aging

preweaning lethality, incomplete penetrance ( J:234643 )

• mice are obtained at a slightly lower than the expected number (10 versus 14.5) based on the Mendelian ratio; time of lethality is not specified

growth/size/body

decreased body weight ( J:234643 )

• mice attain ~40% of normal weight at 3 weeks of age

postnatal growth retardation ( J:234643 )

• mice appear normal at birth but fail to thrive, similar to Bub1b^tm1Jvd homozygotes

homeostasis/metabolism

hypoglycemia ( J:234643 )

• mice exhibit hypoglycemia in the fed state, similar to Bub1b^tm1Jvd homozygotes and opposite to Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

improved glucose tolerance ( J:234643 )

• mice exhibit increased glucose tolerance, similar to Bub1b^tm1Jvd homozygotes and opposite to Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

increased insulin sensitivity ( J:234643 )

• mice exhibit increased insulin sensitivity, similar to Bub1b^tm1Jvd homozygotes and opposite to Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

liver/biliary system

abnormal hepatocyte morphology ( J:234643 )

• at 2 months of age, the cell and nuclear sizes of hepatocytes in male mice are larger than those in single knockout mice

increased hepatocyte karyomegaly ( J:234643 )

cellular

increased hepatocyte karyomegaly ( J:234643 )

polyploidy ( J:234643 )

• mice exhibit an increased percentage of hepatocytes with 8N or greater DNA content, indicating a striking ploidy change

Genotype
MGI:5532534

cn143

• Allelic Composition: Coq7^tm1Hek/Coq7^tm2Hek; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NTac

mortality/aging

mortality/aging ( J:202240 )

N • mice exhibit normal mortality

liver/biliary system

liver/biliary system phenotype ( J:202240 )

N • mice exhibit normal liver morphology

abnormal liver physiology ( J:202240 )

• mild reduction in respiratory capacity in liver mitochondria

• however, a diet supplemented with dietary ubiquinine rescues respiratory chain function

cellular

abnormal respiratory electron transport chain ( J:202240 )

• mild reduction in respiratory capacity in liver mitochondria

• however, a diet supplemented with dietary ubiquinine rescues respiratory chain function

Genotype
MGI:3641135

cn144

• Allelic Composition: Acaca^tm2Sjw/Acaca^tm2Sjw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * FVB

liver/biliary system

decreased liver triglyceride level ( J:110200 )

• on a normal diet liver levels are about 40% lower than in wild-type

decreased susceptibility to hepatic steatosis ( J:110200 )

• after being on a fat free diet for 10 days lipid accumulation in the liver is 66% lower than in wild-type; however fat pad weight is similar to wild-type

• however, when fed a high fat high carbohydrate diet fatty liver development is similar to wild-type

abnormal liver physiology ( J:110200 )

• in cultured hepatocytes the rate of fatty acid synthesis is about 50% of wild-type

• liver acetyl-CoA carboxylase activity is reduced by about 75%

homeostasis/metabolism

decreased circulating ketone body level ( J:110200 )

• on a high fat high carbohydrate but not on a standard chow diet

abnormal glucose homeostasis ( J:110200 )

hyperglycemia ( J:110200 )

• on a high fat high carbohydrate diet blood glucose is increased to 185 +/- 7 mg/dl compared to 155 +/-8 mg/dl for wild-type mice

• however, on a standard diet blood glucose levels are similar

increased circulating insulin level ( J:110200 )

• after being on a fat free diet for 10 days insulin levels are increased but blood glucose is similar to wild-type

abnormal lipid level ( J:110200 )

increased circulating free fatty acids level ( J:110200 )

• on a high fat high carbohydrate nonesterified fatty acid levels are increased by about 30% compared to wild-type mice

decreased fatty acids level ( J:110200 )

• after being on a fat free diet for 10 days liver levels of saturated and monounsaturated fatty acids are significantly lower than in wild-type; however overall liver lipid composition is similar

decreased circulating free fatty acids level ( J:110200 )

• on a normal diet or when fed a fat free diet for 10 days

decreased liver triglyceride level ( J:110200 )

• on a normal diet liver levels are about 40% lower than in wild-type

abnormal enzyme/coenzyme activity ( J:110200 )

• liver acetyl-CoA carboxylase activity is reduced by about 75%

Genotype
MGI:5426955

cn145

• Allelic Composition: Soat2^tm1.1Llr/Soat2^tm1.1Llr; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * DBA

homeostasis/metabolism

decreased circulating cholesterol level ( J:184908 )

• in mice fed a 0.05% cholesterol diet

decreased circulating LDL cholesterol level ( J:184908 )

• in mice fed a 0.05% cholesterol diet

decreased circulating VLDL cholesterol level ( J:184908 )

• in mice fed a 0.1% or 0.5% dietary cholesterol

increased circulating triglyceride level ( J:184908 )

• regardless of dietary cholesterol percentage

decreased liver cholesterol level ( J:184908 )

• total cholesterol and cholesteryl ester regardless of dietary cholesterol percentage

• free cholesterol when fed a 0.5% cholesterol diet

decreased liver triglyceride level ( J:184908 )

• when fed a 0.5% cholesterol diet

liver/biliary system

decreased liver cholesterol level ( J:184908 )

• total cholesterol and cholesteryl ester regardless of dietary cholesterol percentage

• free cholesterol when fed a 0.5% cholesterol diet

decreased liver triglyceride level ( J:184908 )

• when fed a 0.5% cholesterol diet

digestive/alimentary system

digestive/alimentary phenotype ( J:184908 )

N • mice exhibit normal cholesterol absorption

Genotype
MGI:3797770

cn146

• Allelic Composition: Nr5a2^tm1Sakl/Nr5a2^tm1Sakl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * DBA

homeostasis/metabolism

decreased circulating cholesterol level ( J:135822 )

decreased circulating aspartate transaminase level ( J:135822 )

liver/biliary system

abnormal bile composition ( J:135822 )

• bile contains higher concentrations of tauromuricholic acids, taurochenodeoxycholic acid, alpha/omega muricholic acid, and beta-muricholic acid and lower concentrations of taurocholic acid and taurodeoxycholic acid compared to bile in wild-type mice

Genotype
MGI:6119462

cn147

• Allelic Composition: Tmem30a^tm1.1Xjz/Tmem30a^tm1.1Xjz; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6J * DBA

liver/biliary system

bile duct proliferation ( J:249038 )

• according to Krt19 activity

liver inflammation ( J:249038 )

• significant lymphocyte and macrophage infiltration

• increased serum levels of Il6, Il18, Il10, Ifng, and Tnf

abnormal liver morphology ( J:249038 )

• more multinucleate hepatocytes and smaller hepatocytes when fed 0.5% sodium cholate-supplemented diet

decreased liver weight ( J:249038 )

• when fed 0.5% sodium cholate-supplemented diet

• when fed standard chow

liver fibrosis ( J:249038 )

• increased levels of Col1a1, Col3a1 and Tgfb

• exacerbated when fed 0.5% sodium cholate-supplemented diet

intrahepatic cholestasis ( J:249038 )

jaundice ( J:249038 )

• yellow serum at age 2 months on standard chow

• when fed 0.5% sodium cholate-supplemented diet

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:249038 )

N • serum gamma-glutamyl transferase levels

N • plasma creatinine, blood urea nitrogen, and uric acid levels on normal chow or 0.5% sodium cholate-supplemented diet

increased circulating bilirubin level ( J:249038 )

• exacerbated when fed 0.5% sodium cholate-supplemented diet

• approximately 15-fold higher serum total bilirubin (TBIL) levels

• mainly increase in direct bilirubin (DBIL) levels; indirect bilirubin (IBIL) levels only slightly increased

increased circulating alanine transaminase level ( J:249038 )

• exacerbated when fed 0.5% sodium cholate-supplemented diet

increased circulating aspartate transaminase level ( J:249038 )

• exacerbated when fed 0.5% sodium cholate-supplemented diet

increased bile salt level ( J:249038 )

• approximately 20-fold higher serum total bile acid (TBA) levels

• dramatically increased serum unconjugated and conjugated bile acid levels; only small changes in hepatic and biliary bile salt species

• exacerbated when fed 0.5% sodium cholate-supplemented diet

increased alkaline phosphatase activity ( J:249038 )

• elevated plasma Alpl levels

• exacerbated when fed 0.5% sodium cholate-supplemented diet

growth/size/body

growth/size/body region phenotype ( J:249038 )

N • cellular morphology of heart, kidney, lung, spleen, muscle, pancreas, and intestine when fed regular chow or 0.5% sodium cholate-supplemented diet

cachexia ( J:249038 )

• when fed 0.5% sodium cholate-supplemented diet

endocrine/exocrine glands

bile duct proliferation ( J:249038 )

• according to Krt19 activity

immune system

liver inflammation ( J:249038 )

• significant lymphocyte and macrophage infiltration

• increased serum levels of Il6, Il18, Il10, Ifng, and Tnf

behavior/neurological

slow movement ( J:249038 )

• when fed 0.5% sodium cholate-supplemented diet

skeleton

abnormal spine curvature ( J:249038 )

• when fed 0.5% sodium cholate-supplemented diet

Genotype
MGI:5427004

cn148

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her; Nr1h3^tm1.1Djm/Nr1h3^tm1.1Djm; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * DBA

Atherosclerosis lesion area is increased in Ldlr^tm1Her/Ldlr^tm1Her Nr1h3^tm1.1Djm/Nr1h3^tm1.1Djm Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice and TO901317 treatment reduces these lesions

homeostasis/metabolism

decreased circulating triglyceride level ( J:184536 )

• by 4 weeks in mice fed a western diet

abnormal cholesterol homeostasis ( J:184536 )

• mice fed a western diet and treated with T0901317 (an Lxr/Nr1h3 agonist) exhibit impaired reverse cholesterol transport compared with control mice

decreased circulating cholesterol level ( J:184536 )

• by 4 weeks in mice fed a western diet

increased liver cholesterol level ( J:184536 )

• in mice fed a western diet at the conclusion of the experiment

decreased physiological sensitivity to xenobiotic ( J:184536 )

• mice fed a western diet and treated with T0901317 (an Lxr/Nr1h3 agonist) fail to exhibit a change in plasma lipid levels or an increase in fecal excretion of macrophage-derived sterols but an increase in hepatic sterols compared with control mice

• however, treatment with T0901317 reduces atherosclerosis as in controls

liver/biliary system

increased liver cholesterol level ( J:184536 )

• in mice fed a western diet at the conclusion of the experiment

cardiovascular system

increased susceptibility to atherosclerosis ( J:184536 )

• mice fed a western diet exhibit increase in lesion size as detected by macrophage staining compared with control mice

• however, collagen staining or lesions is normal and treatment with T0901317 reduces atherosclerosis as in controls

Genotype
MGI:3847955

cn149

• Allelic Composition: Nr0b2^tm1Mjev/Nr0b2^tm1Mjev; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEvBrd * C57BL/6 * DBA

homeostasis/metabolism

decreased circulating cholesterol level ( J:149005 )

• when fed a high cholesterol diet with cholic acid diet

decreased circulating LDL cholesterol level ( J:149005 )

• either when fed a high cholesterol diet with cholic acid diet or an iodine-deficient diet compared to similarly treated Nr0b2^tm1Mjev homozygotes

Genotype
MGI:4879104

cn150

• Allelic Composition: Rptor^tm1.1Dmsa/Rptor^tm1.1Dmsa; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6 * DBA

liver/biliary system

abnormal hepatocyte morphology ( J:167208 )

• decrease in hepatocyte size

small liver ( J:167208 )

• about a 40% decrease in liver mass compared to controls

abnormal liver physiology ( J:167208 )

• decrease in liver protein content

• fasting does not decrease the size of the liver, unlike in controls

homeostasis/metabolism

increased circulating ketone body level ( J:167208 )

• at early times after refeeding compared to wild-type controls

• feeding mice sodium octanoate after a fast results in prolonged elevation of ketone levels

• aged mice do not display a reduction in ketone production during fasting unlike in aged wild-type controls

Genotype
MGI:5427002

cn151

• Allelic Composition: Nr1h3^tm1.1Djm/Nr1h3^tm1.1Djm; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6 * DBA

homeostasis/metabolism

abnormal lipid homeostasis ( J:184536 )

• mice treated with T0901317 (an Lxr/Nr1h3 agonist) exhibit an attenuated increase in plasma triglycerides, hepatic triglycerides, biliary cholesterol, biliary cholesterol secretion and fecal neutral sterols but an attenuated decrease in CAMCA bile acid composition and cholesterol absorption compared with control mice

increased liver cholesterol level ( J:184536 )

• in mice fed a 2% cholesterol diet

decreased physiological sensitivity to xenobiotic ( J:184536 )

• mice treated with T0901317 (an Lxr/Nr1h3 agonist) exhibit an attenuated increase in plasma triglycerides and cholesterol, hepatic triglycerides, biliary cholesterol, biliary cholesterol secretion and fecal neutral sterols and attenuated decrease in CAMCA bile acid composition, cholesterol absorption and hepatic cholesterol compared with control mice

liver/biliary system

increased liver weight ( J:184536 )

• in mice fed a 2% cholesterol diet

increased liver cholesterol level ( J:184536 )

• in mice fed a 2% cholesterol diet

growth/size/body

increased liver weight ( J:184536 )

• in mice fed a 2% cholesterol diet

Genotype
MGI:5315714

cn152

• Allelic Composition: Commd1^tm2.1Bvds/Commd1^tm2.1Bvds; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6 * DBA * SJL

homeostasis/metabolism

increased liver copper level ( J:182331 )

• in mice fed standard chow at 6 weeks of age but not 9, 12, 34, 46 and 58 weeks

• in mice fed a high copper diet at 28, 40 and 52 weeks

liver/biliary system

increased liver copper level ( J:182331 )

• in mice fed standard chow at 6 weeks of age but not 9, 12, 34, 46 and 58 weeks

• in mice fed a high copper diet at 28, 40 and 52 weeks

Genotype
MGI:3703883

cn153

• Allelic Composition: Smad2^tm1.1Epb/Smad2^tm1.1Epb; Smad3^tm1Cxd/Smad3^tm1Cxd; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * DBA * SJL

liver/biliary system

liver/biliary system phenotype ( J:119642 )

N • mice exhibit normal postnatal liver and body growth and function

cellular

abnormal cell morphology ( J:119642 )

• only a few hepatocytes attach with atypical morphology after seeding

abnormal cell physiology ( J:119642 )

• isolated primary hepatocytes show decreased viability immediately upon isolation, prior to plating (<70% viable cells) compared to controls or other mutant genotypes

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:119642 )

• injection of CCL4 to the liver induces a greater degree of liver injury in mice compared to control or individual single knockout mice; advanced bridging central injury is induced in livers

Genotype
MGI:5607406

cn154

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her; Nr5a2^tm1Sjns/Nr5a2^tm1Sjns; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * C57BL/6J * DBA

cardiovascular system

cardiovascular system phenotype ( J:215556 )

N • mice fed a high-cholesterol diet for 12 weeks exhibit a similar body and liver weight as single Ldlr homozygotes and do not develop increased atherosclerosis

digestive/alimentary system

abnormal feces lipid level ( J:215556 )

• reverse cholesterol transport analysis indicates an increase in fecal sterol content compared to single Ldlr homozygote

homeostasis/metabolism

abnormal feces lipid level ( J:215556 )

• reverse cholesterol transport analysis indicates an increase in fecal sterol content compared to single Ldlr homozygote

abnormal sterol level ( J:215556 )

• reverse cholesterol transport analysis indicates an increase in fecal sterol content compared to single Ldlr homozygotes

Genotype
MGI:3795373

cn155

• Allelic Composition: Igf2r^tm1Rlj/Igf2r⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:80932 )

N • no histologic differences are detected

normal phenotype

no abnormal phenotype detected ( J:80932 )

• mice show no significant differences from wild-type in body or organ weights

cellular

genetic imprinting ( J:80932 )

• the paternally-inherited Igf2r allele is normally silenced through genomic imprinting so embryos inheriting the floxed Igf2r allele maternally are functionally liver-specific homozygous knockouts

Genotype
MGI:3703880

cn156

• Allelic Composition: Smad2^tm1.1Epb/Smad2^tm1.1Epb; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA * SJL

liver/biliary system

liver/biliary system phenotype ( J:119642 )

N • mice exhibit normal postnatal liver and body growth and function

abnormal hepatocyte morphology ( J:119642 )

• after attachment to culture dishes, hepatocytes are elongated with process formation and cell separation compared to wild-type cells which have a cobblestone epithelial morphology

abnormal hepatocyte physiology ( J:119642 )

• hepatocytes express much higher levels of vimentin (mesenchymal marker) compared to control or Smad3 mutant cells

increased hepatocyte proliferation ( J:119642 )

• in culture, untreated cells exhibit ~3-fold greater proliferation compared to controls and Smad3 hepatocytes; after TGFbeta treatement, cells show reduced proliferation compared to controls

• in CCL4-injured livers, cell proliferation is higher at earlier time points than in controls or Smad3-deficient livers

cellular

abnormal cell differentiation ( J:119642 )

• hepatocytes dedifferentiate spontaneously to acquire mesenchymal and promigratory features in culture

abnormal cell migration ( J:119642 )

• compared to wild-type cells which cannot migrate to the wound area in a scratch-wound in vitro assay after 24 hours or only partial cover area when treated with TGFbeta, mutant cells cover the entire scratch area in absence of TGFbeta

increased hepatocyte proliferation ( J:119642 )

• in culture, untreated cells exhibit ~3-fold greater proliferation compared to controls and Smad3 hepatocytes; after TGFbeta treatement, cells show reduced proliferation compared to controls

• in CCL4-injured livers, cell proliferation is higher at earlier time points than in controls or Smad3-deficient livers

Genotype
MGI:4868455

cn157

• Allelic Composition: Ptpn11^tm3Bgn/Ptpn11^tm3Bgn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * C57BL/6J * DBA

homeostasis/metabolism

decreased circulating glucose level ( J:167406 )

• in fasted and fed mice

• following insulin injection

decreased circulating insulin level ( J:167406 )

• in fasted mice

decreased circulating triglyceride level ( J:167406 )

• in fasted mice

improved glucose tolerance ( J:167406 )

• mice exhibit increased ability to clear glucose during a glucose tolerance test compared with wild-type mice

increased insulin sensitivity ( J:167406 )

Genotype
MGI:3522661

cn158

• Allelic Composition: Foxm1^tm1Rhc/Foxm1^tm1Rhc; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA

neoplasm

decreased incidence of tumors by chemical induction ( J:89472 )

• after diethylnitrosamine (DEN) and phenobarbitol (PB) treatment, no adenomas were observed in liver sections from these mice at 23, 33 and 50 weeks of age in contrast to controls

decreased liver tumor incidence ( J:89472 )

• after diethylnitrosamine (DEN) and phenobarbitol (PB) treatment, no adenomas were observed in liver sections from these mice at 23, 33 and 50 weeks of age in contrast to controls

liver/biliary system

abnormal hepatocyte morphology ( J:81015 , J:89472 )

• hepatocyte hypertrophy and compensatory increase in liver size at 7 days after partial hepatectomy (J:81015)

• hypertrophy of hepatocytes was observed at 23 weeks after diethylnitrosamine (DEN) and phenobarbitol (PB) treatment; hepatocytes exhibited a significant reduction in DNA replication and mitosis (J:89472)

decreased liver tumor incidence ( J:89472 )

• after diethylnitrosamine (DEN) and phenobarbitol (PB) treatment, no adenomas were observed in liver sections from these mice at 23, 33 and 50 weeks of age in contrast to controls

abnormal liver regeneration ( J:81015 )

• after partial hepatectomy, hepatocytes exhibited a significant reduction in DNA replication and mitosis; changes in expression levels of cell cycle proteins were observed

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:89472 )

• after diethylnitrosamine (DEN) and phenobarbitol (PB) treatment, no adenomas were observed in liver sections from these mice at 23, 33 and 50 weeks of age in contrast to controls

Genotype
MGI:3615115

cn159

• Allelic Composition: Prkaca^tm3Gsm/Prkaca^tm3Gsm; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

growth/size/body

decreased body size ( J:103418 )

• mice are 10-15% smaller than controls

decreased body length ( J:103418 )

• shorter crown-anus length than controls

liver/biliary system

decreased liver glycogen level ( J:103418 )

• both fed and fasted/refed mutant mice show significantly lower levels of liver glycogen than controls

• fasted mice show similar levels of liver glycogen to controls

homeostasis/metabolism

increased circulating triglyceride level ( J:103418 )

• significant elevation consistent with decreased insulin levels

abnormal glucose homeostasis ( J:103418 )

decreased insulin secretion ( J:103418 )

• a decrease in serum insulin after glucose challenge occurs in contrast to an increase in control mice

• insulin clearance appears to be unaffected

• isolated pancreatic islets are defective in the ability to secrete insulin by glucose stimulation at all concentrations tested ; such islets contain more isulin than control islets, suggesting that the defect is in secretion and not in synthesis or storage

increased circulating glucose level ( J:103418 )

• fasting and fed state blood glucose levels are 25% higher than controls

• mice that are fasted then refed for 6 hours exhibit normal blood glucose levels

decreased circulating insulin level ( J:103418 )

• fasting insulin levels are lower than controls

• slight elevation is seen after a 6 hour refeeding period

• normal insulin sensitivity is seen at two different doses of insulin

impaired glucose tolerance ( J:103418 )

• mutant animals exhibit an impaired ability to remove glucose from the bloodstream after intraperitoneal glucose injection

abnormal glycogen homeostasis ( J:103418 )

• reductions in the levels of fructose-2,6-bisphosphate in the fed state; lower levels are thought to promote gluconeogenesis rather than glycolysis

• in the fed state, level of glucokinase transcripts are reduced; glucokinase regulates glycolysis in the liver

decreased liver glycogen level ( J:103418 )

• both fed and fasted/refed mutant mice show significantly lower levels of liver glycogen than controls

• fasted mice show similar levels of liver glycogen to controls

endocrine/exocrine glands

decreased insulin secretion ( J:103418 )

• a decrease in serum insulin after glucose challenge occurs in contrast to an increase in control mice

• insulin clearance appears to be unaffected

• isolated pancreatic islets are defective in the ability to secrete insulin by glucose stimulation at all concentrations tested ; such islets contain more isulin than control islets, suggesting that the defect is in secretion and not in synthesis or storage

adipose tissue

adipose tissue phenotype ( J:103418 )

N • no differences in the percent adiposity (fat pad weight by total body weight) is detected

Genotype
MGI:3575312

cn160

• Allelic Composition: Nfe2l1^tm1Jefc/Nfe2l1^tm1Ywk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

neoplasm

increased hepatocellular carcinoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

increased liver adenoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

homeostasis/metabolism

increased circulating alanine transaminase level ( J:97188 )

• at 4 weeks

immune system

liver inflammation ( J:97188 )

• infiltration of inflammatory cells are seen in 4 weeks old mutant mice liver

liver/biliary system

liver inflammation ( J:97188 )

• infiltration of inflammatory cells are seen in 4 weeks old mutant mice liver

hepatic necrosis ( J:97188 )

• note: apoptotic cells and necrosis are seen in 4 weeks old mutant mice liver

hepatic steatosis ( J:97188 )

• at 4 weeks, fatty vacuolated cells in liver had a 3-fold elevation in triglyceride levels

• lipid accumulation was also seen in cultures of primary hepatocytes derived from mutant mice

increased hepatocellular carcinoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

increased liver adenoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

liver fibrosis ( J:97188 )

• pericentral and pericellular fibrosis was seen in older animals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:97188

Genotype
MGI:5605688

cn161

• Allelic Composition: Srsf3^tm1Pjln/Srsf3^tm1Pjln; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: BALB/c * C57BL/6 * DBA

mortality/aging

perinatal lethality, incomplete penetrance ( J:205756 )

• many pups die perinatally

postnatal lethality, incomplete penetrance ( J:205756 )

• fewer than the expected Mendelian ratio of pups is seen at weaning (only 17 out of 277 total pups)

growth/size/body

decreased susceptibility to diet-induced obesity ( J:205756 )

• mice fed a high-fat diet are slightly leaner than wild-type mice, although both show hepatic steatosis

decreased body size ( J:205756 )

• pups are smaller at 2 days of age

• surviving mice have reduced body mass at 1 month of age, however by 4 months of age, mice weight the same as wild-type mice

liver/biliary system

increased hepatocyte apoptosis ( J:205756 )

• 30% increase in apoptosis in livers at 1 month of age

abnormal hepatobiliary system development ( J:205756 )

• reduction in the number of binuclear hepatocytes and tetraploidy suggest impaired hepatic differentiation and maturation

• livers show continued presence of hematopoietic cells at 1 month of age unlike in wild-type mice which show only residual CD45-positive hematopoietic cells, however, numbers of circulating blood cells are normal indicating a defect in hepatocyte maturation rather than increase in extramedullary hematopoiesis

abnormal liver morphology ( J:205756 )

• livers of surviving mice exhibit a roughened surface and multiple small nodules

• architecture of the liver is disturbed with large irregular hepatocytes, compressed sinusoidal spaces and bile canaliculi and clusters of small hematopoietic cells

• decrease in lipid droplets in the liver of 1 month old mice

abnormal liver sinusoid morphology ( J:205756 )

• compressed sinusoidal spaces

decreased liver glycogen level ( J:205756 )

• 60% decrease in stored glycogen in the liver

decreased liver cholesterol level ( J:205756 )

• decrease in cholesterol in the liver at 1 month of age but not at 4 months of age

decreased liver triglyceride level ( J:205756 )

• mice fed a high-fat diet do not show an increase in hepatic triglyceride levels as is seen in wild-type mice

abnormal bile canaliculus morphology ( J:205756 )

• compressed bile canaliculi

abnormal hepatocyte morphology ( J:205756 )

• hepatocytes are larger with irregularly sized nuclei and dense mitotic figures

• reduction in the number of binuclear hepatocytes and tetraploidy suggesting impaired hepatic differentiation and maturation

small liver ( J:205756 )

• surviving mice have smaller livers at 1 month of age

pale liver ( J:205756 )

• surviving mice have pale livers at 1 month of age

homeostasis/metabolism

decreased fatty acid oxidation ( J:205756 )

• decrease in fatty acid oxidation in the liver

decreased susceptibility to diet-induced obesity ( J:205756 )

• mice fed a high-fat diet are slightly leaner than wild-type mice, although both show hepatic steatosis

increased circulating bilirubin level ( J:205756 )

hypoglycemia ( J:205756 )

• mice exhibit fasting-induced hypoglycemia at 1 month of age however, fasting insulin levels are normal

• by 4 months of age, fasting blood glucose levels are normal

decreased circulating insulin-like growth factor I level ( J:205756 )

increased circulating growth hormone level ( J:205756 )

decreased circulating cholesterol level ( J:205756 )

• serum cholesterol is lower at 1 month of age on a normal diet and at 4 months of age on the high-fat diet

decreased circulating HDL cholesterol level ( J:205756 )

• at 1 month of age

decreased circulating triglyceride level ( J:205756 )

• serum triglyceride levels are lower on a normal diet and are unchanged on a high-fat diet

increased circulating alanine transaminase level ( J:205756 )

increased circulating alkaline phosphatase level ( J:205756 )

increased circulating aspartate transaminase level ( J:205756 )

decreased circulating serum albumin level ( J:205756 )

• total serum protein is decreased due to a 30% decrease in serum albumin

• however, blood urea nitrogen, calcium, and creatinine are normal

abnormal glucose tolerance ( J:205756 )

• glucose tolerance tests at 4 months of age in mice fed a low-fat diet for 12 weeks show decreased glucose at 15 min but normal values at subsequent times

decreased liver glycogen level ( J:205756 )

• 60% decrease in stored glycogen in the liver

increased insulin sensitivity ( J:205756 )

• insulin tolerance tests at 4 months of age in mice fed a low-fat diet for 12 weeks show increased insulin sensitivity and an inability to correct insulin-induced hypoglycemia

• mice fed a high-fat diet for 12 weeks show increased insulin sensitivity compared to wild-type mice, with a greater drop in blood glucose during the insulin tolerance test

decreased liver cholesterol level ( J:205756 )

• decrease in cholesterol in the liver at 1 month of age but not at 4 months of age

decreased liver triglyceride level ( J:205756 )

• mice fed a high-fat diet do not show an increase in hepatic triglyceride levels as is seen in wild-type mice

adipose tissue

decreased brown adipose tissue amount ( J:205756 )

cardiovascular system

abnormal liver sinusoid morphology ( J:205756 )

• compressed sinusoidal spaces

cellular

abnormal endoplasmic reticulum morphology ( J:205756 )

• the rough endoplasmic reticulum (ER) is dilated in the liver, indicating ER stress

increased hepatocyte apoptosis ( J:205756 )

• 30% increase in apoptosis in livers at 1 month of age

decreased fatty acid oxidation ( J:205756 )

• decrease in fatty acid oxidation in the liver

endocrine/exocrine glands

abnormal thymus development ( J:205756 )

• impaired thymic development

hematopoietic system

abnormal thymus development ( J:205756 )

• impaired thymic development

immune system

abnormal thymus development ( J:205756 )

• impaired thymic development

renal/urinary system

abnormal kidney development ( J:205756 )

• impaired kidney development

Genotype
MGI:6119620

cn162

• Allelic Composition: Cluh^tm1.1Eir/Cluh^tm1.1Eir; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: BALB/cJ * C57BL/6 * DBA * SJL

homeostasis/metabolism

abnormal homeostasis ( J:249661 )

• accumulation of beta-aminoisobutyric acid (BAIB) after 24 hours of starvation

• severely impaired production of ketone body beta-hydroxybutyrate after 24 hours of starvation

• increased lipid droplet levels in liver after 24 hours of starvation

abnormal circulating amino acid level ( J:249661 )

• increased levels of proline, serine, threonine, methionine, and lysine in serum after 24 hours of starvation

increased circulating lysine level ( J:249661 )

• increased lysine level in serum after 24 hours of starvation

increased circulating methionine level ( J:249661 )

• increased methionine level in serum after 24 hours of starvation

increased circulating proline level ( J:249661 )

• increased proline level in serum after 24 hours of starvation

increased circulating serine level ( J:249661 )

• increased serine level in serum after 24 hours of starvation

increased circulating threonine level ( J:249661 )

• increased threonine level in serum after 24 hours of starvation

decreased fasting circulating glucose level ( J:249661 )

• after 24 hours of starvation

hypoglycemia ( J:249661 )

increased circulating alanine transaminase level ( J:249661 )

• slight increase in serum at age 8 weeks

liver/biliary system

liver/biliary system phenotype ( J:249661 )

N • no liver fibrosis or inflammation

abnormal hepatocyte mitochondrial morphology ( J:249661 )

• mitochondrial clustering in liver at age 8 weeks

abnormal liver physiology ( J:249661 )

• increased lipid droplet levels in liver after 24 hours of starvation

• depletion of alanine-glyoxylate aminotransferase 2 (Agxt2) after 24 hours of starvation

• severely impaired production of ketone body beta-hydroxybutyrate after 24 hours of starvation

• accumulation of beta-aminoisobutyric acid (BAIB) after 24 hours of starvation

cellular

abnormal hepatocyte mitochondrial morphology ( J:249661 )

• mitochondrial clustering in liver at age 8 weeks

increased apoptosis ( J:249661 )

• trend to increase in apoptotic cells in liver at age 8 weeks

abnormal cellular respiration ( J:249661 )

• reduction in rate of maximal respiration after dissipation of membrane potential with carbonyl cyanide m-chlorophenyl hydrazone (CCCP)

adipose tissue

increased brown fat lipid droplet number ( J:249661 )

• in liver after 24 hours of starvation

Genotype
MGI:5607591

cn163

• Allelic Composition: Lman1^{tm1c(KOMP)Wtsi}/Lman1^{tm1c(KOMP)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N

homeostasis/metabolism

abnormal blood homeostasis ( J:213133 )

• mice show a reduction of plasma coagulation factor V (FV) activity and a reduction in plasma FV antigen level

• however plasma coagulation factor VIII (FVIII) levels are normal

Genotype
MGI:5903311

cn164

• Allelic Composition: Mpc1^{tm1c(EUCOMM)Wtsi}/Mpc1^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:236662 )

N • mice exhibit normal alanine and aspartate transaminase levels, glucose and insulin tolerance

increased fatty acid oxidation ( J:236662 )

• hepatic and whole-body

decreased circulating glucose level ( J:236662 )

• after 9 weeks on a high-fat diet

increased circulating ketone body level ( J:236662 )

• in mice fed standard chow or a high-fat diet

increased circulating lactate level ( J:236662 )

• slightly in mice fed normal chow

• fasting lactate in mice fed a high-fat diet

decreased circulating cholesterol level ( J:236662 )

decreased circulating triglyceride level ( J:236662 )

• fasting

decreased respiratory quotient ( J:236662 )

• during the dark cycle when most physically active

abnormal gluconeogenesis ( J:236662 )

• impaired pyruvate-driven gluconeogenesis

• however, hepatic glycogen levels are normal

improved glucose tolerance ( J:236662 )

• in mice fed a high-fat diet

• however, insulin tolerance is the same as in controls

increased triglyceride level ( J:236662 )

• slightly increased postabsorptive triglycerides when fed normal chow

• increased postabsorptive triglycerides in mice fed a high-fat diet

• however, liver triglycerides are normal

cellular

abnormal mitochondrial physiology ( J:236662 )

• mitochondria exhibit a complete loss of pyruvate uptake compared with control mice

increased fatty acid oxidation ( J:236662 )

• hepatic and whole-body

growth/size/body

decreased body weight ( J:236662 )

• slightly

• however, body composition are normal

behavior/neurological

behavior/neurological phenotype ( J:236662 )

N • mice exhibit normal food intake and voluntary physical activity

Genotype
MGI:7531058

cn165

• Allelic Composition: Thrap3^{tm1c(KOMP)Wtsi}/Thrap3^{tm1c(KOMP)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA
• Cell Lines: EPD0814_5_G12

growth/size/body

decreased body weight ( J:339439 )

• mice fed a high-fat diet (HFD) for 12 weeks exhibit a significantly lower body weight than HFD-fed control mice

• however, body weight is normal under normal chow diet (NCD) conditions

homeostasis/metabolism

abnormal autophagosome formation ( J:339439 )

• livers from HFD-fed mice exhibit a significantly higher number of autophagic structures (autophagosomes/autolysosomes) than livers from diet-matched controls

abnormal mitophagy ( J:339439 )

• most of the increased LC3 puncta in FFA-treated hepatocytes colocalize with MitoTracker (a mitochondrial-specific dye), indicating enhanced mitophagy; PINK1 (a marker protein of mitophagy) is increased in the liver

enhanced autophagy ( J:339439 )

• liver lysates from HFD-fed mice show increased expression of autophagosome proteins MAP1LC3A (LC3), ULK1 and SQSTM1 (p62)

• primary hepatocytes transfected with GFP-LC3 have more LC3 puncta per cell than control hepatocytes

• lysates from primary hepatocytes treated with bafilomycin A1 (BafA1) show significantly more LC3 than BafA1-treated control hepatocytes

decreased circulating glucose level ( J:339439 )

• HFD-fed mice exhibit significantly lower blood glucose levels than diet-matched controls

• however, blood glucose levels are normal under NCD conditions

decreased circulating insulin level ( J:339439 )

• HFD-fed mice exhibit significantly lower serum insulin levels than diet-matched controls

• however, serum insulin levels are normal under NCD conditions

decreased circulating cholesterol level ( J:339439 )

• HFD-fed mice exhibit significantly lower serum cholesterol levels than diet-matched controls

• however, serum cholesterol levels are normal under NCD conditions

decreased circulating free fatty acids level ( J:339439 )

• HFD-fed mice exhibit significantly lower serum FFA levels than diet-matched controls

• however, serum FFA levels are normal under NCD conditions

decreased circulating triglyceride level ( J:339439 )

• HFD-fed mice exhibit significantly lower serum TG levels than diet-matched controls

• however, serum TG levels are normal under NCD conditions

decreased circulating alanine transaminase level ( J:339439 )

• HFD-fed mice exhibit significantly lower serum ALT levels than diet-matched controls

• however, serum ALT levels are normal under NCD conditions

decreased circulating aspartate transaminase level ( J:339439 )

• HFD-fed mice exhibit significantly lower serum AST levels than diet-matched controls

• however, serum AST levels are normal under NCD conditions

increased energy expenditure ( J:339439 )

• HFD-fed mice show a significantly higher energy expenditure than diet-matched controls

increased oxygen consumption ( J:339439 )

• primary hepatocytes from HFD-fed mice show an improved oxygen consumption rate

• HFD-fed mice show a significantly higher oxygen consumption rate (VO2) during day and night

• however, no changes in locomotor activity or food intake are noted under HFD conditions

improved glucose tolerance ( J:339439 )

• HFD-fed mice exhibit improved glucose tolerance relative to diet-matched controls

• however, glucose tolerance is normal under NCD conditions

increased insulin sensitivity ( J:339439 )

• HFD-fed mice exhibit improved insulin sensitivity relative to diet-matched controls

• however, insulin tolerance is normal under NCD conditions

decreased liver cholesterol level ( J:339439 )

• mice fed a HFD or a MCD diet exhibit significantly lower liver cholesterol levels than diet-matched controls

• however, liver cholesterol levels are normal under NCD conditions

decreased liver triglyceride level ( J:339439 )

• mice fed a HFD or a MCD diet exhibit significantly lower liver triglyceride levels than diet-matched controls

• however, liver triglyceride levels are normal under NCD conditions

liver/biliary system

increased hepatocyte mitochondrial DNA content ( J:339439 )

• HFD-fed mice exhibit a significantly higher mtDNA level in the liver than diet-matched controls

decreased liver cholesterol level ( J:339439 )

• mice fed a HFD or a MCD diet exhibit significantly lower liver cholesterol levels than diet-matched controls

• however, liver cholesterol levels are normal under NCD conditions

decreased liver triglyceride level ( J:339439 )

• mice fed a HFD or a MCD diet exhibit significantly lower liver triglyceride levels than diet-matched controls

• however, liver triglyceride levels are normal under NCD conditions

decreased susceptibility to diet-induced hepatic steatosis ( J:339439 )

• mice fed a HFD for 12 weeks exhibit attenuated hepatic steatosis, as indicated by a darker liver color and a significant reduction in liver size, liver weight, hepatic triglyceride and cholesterol level, nonalcoholic fatty liver disease (NAFLD) activity score (NAS), and fibrosis score relative to HFD-fed control mice

• mice fed a methionine/choline-deficient (MCD) diet for 4 weeks also show reduced hepatic steatosis with darker liver color and significantly lower hepatic triglyceride and cholesterol levels, NAS and fibrosis scores than MCD-fed control mice

• however, mice show no differences in liver size, weight or lipid accumulation when fed a normal chow diet (NCD)

abnormal liver physiology ( J:339439 )

• following insulin administration, both HFD-fed and NCD-fed mice show increased phosphorylation of the Ser473 residue of AKT in the liver relative to controls

• however, expression of fatty acid beta-oxidation- and lipogenesis-related genes is not significantly altered

abnormal hepatocyte physiology ( J:339439 )

• primary hepatocytes from HFD-fed mice show a significant increase in the extracellular acidification rate (ECAR)

cellular

increased hepatocyte mitochondrial DNA content ( J:339439 )

• HFD-fed mice exhibit a significantly higher mtDNA level in the liver than diet-matched controls

abnormal mitochondrial crista morphology ( J:339439 )

• HFD-fed mice exhibit a significantly higher cristae volume density in the liver than diet-matched controls

increased mitochondrial size ( J:339439 )

• HFD-fed mice exhibit a significantly greater area of mitochondria in the liver than diet-matched controls

abnormal autophagosome formation ( J:339439 )

• livers from HFD-fed mice exhibit a significantly higher number of autophagic structures (autophagosomes/autolysosomes) than livers from diet-matched controls

abnormal mitophagy ( J:339439 )

• most of the increased LC3 puncta in FFA-treated hepatocytes colocalize with MitoTracker (a mitochondrial-specific dye), indicating enhanced mitophagy; PINK1 (a marker protein of mitophagy) is increased in the liver

enhanced autophagy ( J:339439 )

• liver lysates from HFD-fed mice show increased expression of autophagosome proteins MAP1LC3A (LC3), ULK1 and SQSTM1 (p62)

• primary hepatocytes transfected with GFP-LC3 have more LC3 puncta per cell than control hepatocytes

• lysates from primary hepatocytes treated with bafilomycin A1 (BafA1) show significantly more LC3 than BafA1-treated control hepatocytes

abnormal respiratory electron transport chain ( J:339439 )

• HFD-fed mice show significantly higher levels of mitochondrial respiratory chain complex proteins, such as succinate dehydrogenase complex iron sulfur subunit B (SDHB), cytochrome b-c1 complex subunit 2 (UQCR2), and ATP synthase subunit alpha (ATP5A) in the liver than diet-matched controls

abnormal mitochondrial ATP synthesis coupled electron transport ( J:339439 )

• primary hepatocytes from HFD-fed mice show a significant increase in ATP production

Genotype
MGI:5660646

cn166

• Allelic Composition: Hmox1^tm1.1Hes/Hmox1^tm1.1Hes; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA

cellular

abnormal cellular respiration ( J:214639 )

• primary hepatocytes from high-fat diet fed mice exhibit increased basal, spare as well as maximal respiratory capacity

abnormal mitochondrial physiology ( J:214639 )

• primary hepatocytes from high-fat diet fed mice exhibit increased basal, spare as well as maximal respiratory capacity, however, no changes in coupling efficiency, mitochondrial DNA content, mitochondrial mass or respiratory chain stoichiometry were seen

• increase in oxygen consumption rate of primary hepatocytes from high-fat diet fed mice

abnormal redox activity ( J:214639 )

• an approximate 50% increase in intracellular hydrogen peroxide and an increase of cytosolic reactive oxygen species

homeostasis/metabolism

decreased circulating alanine transaminase level ( J:214639 )

• mice fed a high-fat diet show improved serum levels of alanine transaminase (ALAT), aspartate transaminase (ASAT), and ASAT/ALAT ratios compared to controls, indicating less hepatotoxicity

decreased circulating aspartate transaminase level ( J:214639 )

• mice fed a high-fat diet show improved serum levels of alanine transaminase (ALAT), aspartate transaminase (ASAT), and ASAT/ALAT ratios compared to controls, indicating less hepatotoxicity

increased insulin sensitivity ( J:214639 )

• mice fed a high-fat diet exhibit increased insulin sensitivity

• however, mice fed a high-fat diet show similar weight gain and glucose tolerance as controls

abnormal metabolism ( J:214639 )

• mice exhibit resistance to high-fat diet-induced metabolic disease

• however, mice fed a chow diet develop normally, exhibit normal liver morphology and serum parameters, normal glucose and insulin tolerance

liver/biliary system

decreased susceptibility to diet-induced hepatic steatosis ( J:214639 )

• mice fed a high-fat diet exhibit attenuated liver steatosis compared to controls

Genotype
MGI:5758759

cn167

• Allelic Composition: Glul^tm1.1Geno/Glul^tm1.1Geno; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA

RNA oxidation in Glul^tm1.1Geno/Glul^tm1.1Geno Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mouse brain

mortality/aging

premature death ( J:221031 )

• mice exhibit a slightly reduced life span relative to controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:221031 )

N • mice exhibit normal serum activities of aspartate and alanine aminotransferases indicating absence of liver damage

N • no differences in serum and urine urea nitrogen or serum glutamine, glutamate or alanine concentrations are observed indicating a functional urea cycle

increased circulating ammonia level ( J:221031 )

• significantly elevated plasma ammonia levels at 8-9 weeks and 12-14 months of age

cellular

oxidative stress ( J:221031 )

• induction of oxidative stress in specific brain regions, as shown by increased protein Tyr nitration and RNA oxidation in the cerebellum, hippocampus, and somatosensory cortex, but not in the piriform cortex, relative to controls

• unusually high levels of oxidized RNA in cerebellar Purkinje cells

• however, no evidence of microglia activation or increased synthesis of proinflammatory cytokines in the cerebral cortex

behavior/neurological

abnormal fear-related response ( J:221031 )

• impaired fear memory in the O-Maze test, as shown by increased time spent in the open arms and decreased time spent in the protected (closed) arms relative to controls

hyperactivity ( J:221031 )

• increased total activity time, activity counts, and distance traveled at 24 hrs after transfer into a light barrier-equipped cage relative to controls

liver/biliary system

liver/biliary system phenotype ( J:221031 )

N • mice exhibit intact liver architecture and zonation relative to controls

Genotype
MGI:5613394

cn168

• Allelic Composition: Bmal1^tm1.1Shbi/Bmal1^tm1.1Shbi; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA

behavior/neurological

behavior/neurological phenotype ( J:177865 )

N • mice exhibit normal locomotor activity

liver/biliary system

liver/biliary system phenotype ( J:177865 )

N • mice fed a normal or high fat diet exhibit almost normal liver triglyceride content

Genotype
MGI:5556080

cn169

• Allelic Composition: Sirt3^tm1.1Auw/Sirt3^tm1.1Auw; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207274 )

N • mice fed chow or a high-fat diet exhibit a normal metabolic phenotype

Genotype
MGI:7611637

cn170

• Allelic Composition: Tor1aip2^tm1.1Wtd/Tor1aip2^tm1.1Wtd; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA

liver/biliary system

liver/biliary system phenotype ( J:345574 )

N • livers are grossly normal and do not develop steatosis

N • liver triglyceride levels are similar to controls

normal phenotype

no abnormal phenotype detected ( J:345574 )

• viable with no overt abnormalities

• plasma triglyceride levels are similar to controls

Genotype
MGI:5427446

cn171

• Allelic Composition: Pik3c3^{tm1c(EUCOMM)Wtsi}/Pik3c3^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(CAG-EGFP/Map1lc3b)53Nmz/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * C57BL/6NCrj * DBA

liver/biliary system

abnormal liver physiology ( J:182628 )

• livers from fed and starved exhibit blocked autophagy flux compared with control livers

cellular

abnormal autophagy ( J:182628 )

• livers from fed and starved exhibit blocked autophagy flux compared with control livers

homeostasis/metabolism

abnormal autophagy ( J:182628 )

• livers from fed and starved exhibit blocked autophagy flux compared with control livers

Genotype
MGI:6719088

cn172

• Allelic Composition: Tjp1^tm1.1Whun/Tjp1^tm1.1Whun; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2

liver/biliary system

liver/biliary system phenotype ( J:306936 )

N • mice show normal total and direct bilirubin levels, bile acids, and alkaline phosphatase levels

Genotype
MGI:5805372

cn173

• Allelic Composition: Faf2^tm1Tfji/Faf2^tm1Tfji; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * CBA * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:235325 )

N • mice fed a normal diet exhibit normal levels of alanine and aspartate transaminase and lactacte dehydrogenase

N • mice fed a high-fat diet exhibit normal liver levels of triglyceride, total cholesterol and free cholesterol and insulin sensitivity

decreased circulating free fatty acids level ( J:235325 )

• 0.899-fold in females and 0.853-fold in males when mice are fed a high-fat diet

decreased circulating phospholipid level ( J:235325 )

♂ • in male mice when fed a normal diet

increased circulating phospholipid level ( J:235325 )

♀ • in female mice when fed a normal diet

decreased circulating triglyceride level ( J:235325 )

• 0.665-fold in females and 0.632-fold times in males when mice are fed a high-fat diet

• in mice fed a high-fat diet

decreased circulating VLDL triglyceride level ( J:235325 )

• when mice are fed a high-fat diet

increased circulating alkaline phosphatase level ( J:235325 )

• 1.35-fold in females and 1/27-fold in males when fed a normal diet

• 2.23-fold in females and 1.52-fold in males when mice are fed a high-fat diet

increased circulating aspartate transaminase level ( J:235325 )

• 1.74-fold in females and 1.30-fold in males when mice are fed a high-fat diet

• however, levels are normal in mice fed a normal diet

abnormal apolipoprotein level ( J:235325 )

• reduced ApoB secretion from hepatocytes

liver/biliary system

macrovesicular hepatic steatosis ( J:235325 )

• periportal macroscopic steatosis when mice are fed a high-fat diet, more so in female mice than male mice

growth/size/body

decreased body weight ( J:235325 )

• 0.887-fold in females and 0.897-fold in males when mice are fed a high-fat diet

Genotype
MGI:5427443

cn174

• Allelic Composition: Pik3c3^{tm1c(EUCOMM)Wtsi}/Pik3c3^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA

Liver steatosis in Pik3c3^{tm1c(EUCOMM)Wtsi}/Pik3c3^{tm1c(EUCOMM)Wtsi} Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

mortality/aging

premature death ( J:182628 )

• most mice die within 1 year

liver/biliary system

abnormal liver morphology ( J:182628 )

• mice exhibit intracellular vacuolation and accumulation of lipids unlike in control mice

• fed mice exhibit a large number of small-sized mitochondria unlike control mice

• livers of fasted mice exhibit virtually no autophagosomes and many swollen mitochondria unlike livers from control mice

• livers exhibit increased protein content compared with wild-type livers

enlarged liver ( J:182628 )

decreased liver glycogen level ( J:182628 )

hepatic steatosis ( J:182628 )

pale liver ( J:182628 )

homeostasis/metabolism

decreased liver glycogen level ( J:182628 )

growth/size/body

decreased body size ( J:182628 )

enlarged liver ( J:182628 )

Genotype
MGI:5758892

cn175

• Allelic Composition: Sco1^{tm1c(KOMP)Wtsi}/Sco1^{tm1c(KOMP)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA

mortality/aging

premature death ( J:222036 )

• median life expectancy is 70 days

liver/biliary system

abnormal liver morphology ( J:222036 )

• from P37 onward, livers exhibit changes in quality and consistency of their color (spotty) compared with control mice

decreased liver copper level ( J:222036 )

• as early as P18, worsening with time

increased liver iron level ( J:222036 )

• without necrosis in Kupffer cells at P57

• however, total labile mitochondrial copper pool in the liver or other tissues (heart and brain) is normal

increased liver cholesterol level ( J:222036 )

increased liver triglyceride level ( J:222036 )

hepatic steatosis ( J:222036 )

• from P37 onward

homeostasis/metabolism

increased spleen iron level ( J:222036 )

• in reticuloendothelial cells of the spleen at P57

decreased kidney copper level ( J:222036 )

• modest

decreased liver copper level ( J:222036 )

• as early as P18, worsening with time

increased liver iron level ( J:222036 )

• without necrosis in Kupffer cells at P57

• however, total labile mitochondrial copper pool in the liver or other tissues (heart and brain) is normal

increased liver cholesterol level ( J:222036 )

increased liver triglyceride level ( J:222036 )

hematopoietic system

hematopoietic system phenotype ( J:222036 )

N • red blood cells numbers and properties are normal

decreased leukocyte cell number ( J:222036 )

increased spleen iron level ( J:222036 )

• in reticuloendothelial cells of the spleen at P57

spleen atrophy ( J:222036 )

decreased spleen white pulp amount ( J:222036 )

growth/size/body

decreased body size ( J:222036 )

• after 28 days

weight loss ( J:222036 )

• after 28 days

cellular

increased mitochondrial number ( J:222036 )

• in the liver

abnormal mitochondrial physiology ( J:222036 )

• increased mitochondrial proliferation in the liver

immune system

decreased leukocyte cell number ( J:222036 )

increased spleen iron level ( J:222036 )

• in reticuloendothelial cells of the spleen at P57

spleen atrophy ( J:222036 )

decreased spleen white pulp amount ( J:222036 )

renal/urinary system

decreased kidney copper level ( J:222036 )

• modest

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cytochrome-c oxidase deficiency disease		DOID:3762	OMIM:PS220110	J:222036

Genotype
MGI:6717173

cn176

• Allelic Composition: Zc3h12a^{tm1c(EUCOMM)Hmgu}/Zc3h12a^{tm1c(EUCOMM)Hmgu}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA

liver/biliary system

abnormal bile duct epithelium morphology ( J:304105 )

• mice show the eventual disruption of the bile duct epithelium

bile duct hyperplasia ( J:304105 )

• extensive bile duct hyperplasia at 6 weeks of age

enlarged liver ( J:304105 )

liver inflammation ( J:304105 )

• 6 to 52-week-old mice show extensive parenchymal inflammation

• mice of all ages show increased leukocyte infiltration into the liver parenchyma; the predominant population of leukocytes is T lymphocytes in 6-week-old-mice, while 24-week-old mice show an additional accumulation of B lymphocytes, macrophages and neutrophils

abnormal liver parenchyma morphology ( J:304105 )

• 6 to 52-week-old mice show extensive parenchymal inflammation and parenchymal fibrosis

liver fibrosis ( J:304105 )

• 6 to 52-week-old mice show parenchymal fibrosis and fibrosis in portal areas

abnormal bile duct physiology ( J:304105 )

• active and progressive proliferation of intrahepatic bile ducts is seen in 6 to 52-week-old mice, with intrahepatic and periportal cholangiocyte proliferation

bile duct inflammation ( J:304105 )

• symptoms of primary biliary cholangitis are already seen at P10; intrahepatic bile duct pathology is extensive at 6 weeks, less severe in the liver parenchyma at 24 weeks, and modestly reintensified by 52 weeks

• males and females show the same features of primary biliary cholangitis

intrahepatic cholestasis ( J:304105 )

• mice show bile duct lumen obstruction due to proliferation of bile ducts, bile duct epithelium disruption, inflammation, and fibrosis

endocrine/exocrine glands

abnormal bile duct epithelium morphology ( J:304105 )

• mice show the eventual disruption of the bile duct epithelium

bile duct hyperplasia ( J:304105 )

• extensive bile duct hyperplasia at 6 weeks of age

growth/size/body

enlarged liver ( J:304105 )

enlarged spleen ( J:304105 )

hematopoietic system

enlarged spleen ( J:304105 )

increased IgG level ( J:304105 )

• IgG concentrations are increased at 6- and 24-weeks of age

increased IgM level ( J:304105 )

• IgM concentrations are increased at 6- and 24-weeks of age

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:304105 )

• alkaline phosphatase activity in the serum is increased at 6 weeks of age

increased bile salt level ( J:304105 )

• concentration of total bile acids in the serum is increased at 6 weeks of age

• bile acid deposition in hepatocytes eventually occurs

immune system

enlarged spleen ( J:304105 )

increased IgG level ( J:304105 )

• IgG concentrations are increased at 6- and 24-weeks of age

increased IgM level ( J:304105 )

• IgM concentrations are increased at 6- and 24-weeks of age

increased autoantibody level ( J:304105 )

• 60-90% mice exhibit increased plasma concentrations of anti-PDC-E2 mitochondrial autoantibodies

increased anti-nuclear antigen antibody level ( J:304105 )

• 90% of 12-week-old mice exhibit elevated anti-gp-210 nuclear autoantibodies

granulomatous inflammation ( J:304105 )

• eventually mice show formation of small granulomas in the liver

bile duct inflammation ( J:304105 )

• symptoms of primary biliary cholangitis are already seen at P10; intrahepatic bile duct pathology is extensive at 6 weeks, less severe in the liver parenchyma at 24 weeks, and modestly reintensified by 52 weeks

• males and females show the same features of primary biliary cholangitis

liver inflammation ( J:304105 )

• 6 to 52-week-old mice show extensive parenchymal inflammation

• mice of all ages show increased leukocyte infiltration into the liver parenchyma; the predominant population of leukocytes is T lymphocytes in 6-week-old-mice, while 24-week-old mice show an additional accumulation of B lymphocytes, macrophages and neutrophils

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary biliary cholangitis		DOID:12236	OMIM:PS109720	J:304105

Genotype
MGI:6157293

cn177

• Allelic Composition: Fbxw7^tm1Iken/Fbxw7^tm1Iken; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA

endocrine/exocrine glands

bile duct hyperplasia ( J:258194 )

• hyperplasia of bile ducts throughout the liver at 12 months of age

dilated bile duct ( J:258194 )

• dilatation of bile ducts throughout the liver at 12 months of age

liver/biliary system

bile duct hyperplasia ( J:258194 )

• hyperplasia of bile ducts throughout the liver at 12 months of age

dilated bile duct ( J:258194 )

• dilatation of bile ducts throughout the liver at 12 months of age

Genotype
MGI:5583958

cn178

• Allelic Composition: Secisbp2^{tm1c(EUCOMM)Wtsi}/Secisbp2^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA
• Cell Lines: EPD0052_2_C03

liver/biliary system

liver/biliary system phenotype ( J:213080 )

N • mice exhibit no evidence of liver damage

Genotype
MGI:7414196

cn179

• Allelic Composition: Pcx^{tm1c(EUCOMM)Wtsi}/Pcx^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA * SJL

growth/size/body

growth/size/body region phenotype ( J:332296 )

N • mice exhibit normal body weight under fed or fasted conditions

N • mice fed a high-fat diet for 12 weeks show no difference in body weight gain from controls and no differences in gonadal white adipose tissue, inguinal white adipose tissue, or liver weights

increased susceptibility to weight loss ( J:332296 )

• mice lose body weight after 7 days of ketogenic diet feeding, however kidney and liver weights are normal on a ketogenic diet

increased kidney weight ( J:332296 )

♀ • female, but not male, mice show an increase in kidney weight when fed a high-fat diet

homeostasis/metabolism

abnormal fatty acid oxidation ( J:332296 )

• mice exhibit acceleration of hepatic ketogenesis

abnormal insulin secretion ( J:332296 )

♂ • glucose-invoked insulin production is improved in high-fat diet-fed males

decreased circulating glucose level ( J:332296 )

• mice exhibit suppression of both fed and fasted blood glucose levels, however this small suppression in blood glucose is not likely physiologically significant

• males fed a high-fat diet exhibit a suppression in blood glucose, however triglycerides, cholesterol, and nonesterified fatty acids are unaffected

• fasting high-fat diet-fed males and females exhibit suppression in blood glucose levels

• mice fed a ketogenic diet exhibit a large suppression in blood glucose

• in summary, mice tolerate a 24 hour fast and high-fat diet feeding with normal and improved homeostasis, respectively, but are unable to sustain glucose homeostasis under a ketogenic diet

decreased fasting circulating glucose level ( J:332296 )

• mice exhibit suppression fasted blood glucose levels, however this small suppression in blood glucose is not likely physiologically significant

hypoglycemia ( J:332296 )

• mice fed a ketogenic diet for 1 week become severely hypoglycemic

increased circulating ketone body level ( J:332296 )

• ketone body beta-hydroxybutyrate (BHB) is increased in fed mice but not fasted mice, indicating enhanced ketogenesis

• BHB concentrations are increased in high-fat diet-fed males

• fasting BHB level is increased in high-fat diet-fed males and females without affecting triglyceride or cholesterol concentrations

• males, but not females, fed a ketogenic diet show increased circulating BHB level

increased circulating lactate level ( J:332296 )

• mice exhibit an increase in circulating lactate

• fasting high-fat diet-fed males and females exhibit an increase in blood lactate concentration

• mice fed a ketogenic diet show an exacerbated increase in circulating lactate than under basal conditions

increased circulating free fatty acids level ( J:332296 )

• fasting nonesterified fatty acid (NEFA) level is increased in high-fat diet-fed males and females without affecting triglyceride or cholesterol concentrations

• however, chow-fed mice exhibit normal circulating NEFA and triglyceride levels

• males and females fed a ketogenic diet show increased circulating NEFA levels

increased circulating triglyceride level ( J:332296 )

♂ • males fed a ketogenic diet show increased circulating triglycerides

impaired gluconeogenesis ( J:332296 )

• primary hepatocytes show decreased production of glucose from labeled lactate or glutamine indicating suppressed gluconeogenesis

improved glucose tolerance ( J:332296 )

♂ • high-fat diet-fed males show improved blood glucose tolerance with increased glucose clearance and lower insulin levels indicating protection from high-fat-induced glucose tolerance

♂ • female high-fat diet-fed mice do not exhibit changes in glucose or insulin tolerance

abnormal insulin clearance ( J:332296 )

♂ • insulin tolerance test shows an improvement in insulin-stimulated blood glucose clearance in high-fat diet-fed males

♂ • female high-fat diet-fed mice do not exhibit changes in insulin tolerance

increased liver triglyceride level ( J:332296 )

• liver triglyceride content is increased following a 24 hour fast

abnormal amino acid metabolism ( J:332296 )

♂ • 24 hour fasted males show an increase in liver metabolites, especially urea cycle intermediates including arginiosuccinate, citrulline, and homocitrulline

♂ • almost all N-acetylated forms of free amino acids are elevated in the liver

endocrine/exocrine glands

abnormal insulin secretion ( J:332296 )

♂ • glucose-invoked insulin production is improved in high-fat diet-fed males

cellular

abnormal mitochondrial physiology ( J:332296 )

• fed and fasted mice show an increased abundance of lysine-acetylated mitochondrial proteins in the liver, indicating mitochondrial protein hyperacetylation in liver

• mice fed a high-fat diet exhibit a large increase in the abundance of lysine-acetylated proteins

• however, ketogenic diet-fed mice exhibit a similar pattern of lysine-acetylated proteins as controls

abnormal fatty acid oxidation ( J:332296 )

• mice exhibit acceleration of hepatic ketogenesis

liver/biliary system

increased liver triglyceride level ( J:332296 )

• liver triglyceride content is increased following a 24 hour fast

hepatic steatosis ( J:332296 )

♂ • livers of males fed a ketogenic diet are lipid laden with abundant lipid droplet deposition

abnormal liver physiology ( J:332296 )

♂ • 24 hour fasted males show an increase in liver metabolites, especially urea cycle intermediates including arginiosuccinate, citrulline, homocitrulline, and urea

♂ • almost all N-acetylated forms of free amino acids are elevated in the liver

renal/urinary system

increased kidney weight ( J:332296 )

♀ • female, but not male, mice show an increase in kidney weight when fed a high-fat diet

Genotype
MGI:4456459

cn180

• Allelic Composition: Il6ra^tm1.1Drew/Il6ra^tm1.1Drew; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * SJL

immune system

decreased acute inflammation ( J:160966 )

• acute-phase response to turpentine challenge is completely muted compared to in similarly treated wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:160966 )

N • mice exhibit normal healing of large wounds

Genotype
MGI:5822858

cn181

• Allelic Composition: Lpcat3^{tm1c(EUCOMM)Wtsi}/Lpcat3^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * SJL
• Cell Lines: EPD0455_5_A07

homeostasis/metabolism

abnormal circulating apolipoprotein level ( J:220827 )

• fractionation of plasma lipoproteins revealed lower levels of apolipoprotein B (apoB) in the VLDL fraction of chow-fed mice following an overnight fast

• however, total plasma apoB levels and protein levels of apoB in liver are similar to those in control mice

• increased levels of plasma apoB-100 following a western diet for 9 weeks

abnormal lipid homeostasis ( J:220827 )

• absence of arachidonoyl phospholipids profoundly affects lipid movement within membranes and lipidation of apoB-containing lipoproteins

abnormal lipid level ( J:220827 )

• mice secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl phospholipids

• plasma VLDL particles are markedly smaller and poorly lipidated

• EM analysis of liver samples showed reduced nascent lipoprotein particle size in the lumen of Golgi and secretory vesicles

decreased circulating triglyceride level ( J:220827 )

• decreased plasma triglyceride (TG) levels following an overnight fast on a chow diet

• lower total plasma TG levels following a western diet (40% high fat and 0.2% cholesterol) for 9 weeks

decreased circulating VLDL triglyceride level ( J:220827 )

• TG levels in the VLDL plasma fraction are markedly reduced following an overnight fast

• striking loss of TG in the VLDL plasma lipoprotein fraction following a western diet for 9 weeks

increased liver cholesterol level ( J:220827 )

• prominent accumulation of hepatic cholesterol following a western diet for 9 weeks

• increase in total cholesterol ester and a number of cholesterol ester species on a chow diet, with generally similar results on a western diet

abnormal phospholipid level ( J:220827 )

• ~70% reduction in the abundance of 16:0, 20:4 phosphatidylcholine (PC) and 18:0, 20:4 PC (two of the most abundant arachidonoyl PC species in liver membranes) on a chow diet with compensatory increases in the abundance of other PC species, esp. those containing monounsaturated chains such as 16:0, 18:1 PC and 18:0, 18:1 PC

• increased abundance of certain PC species, such as 16:0, 18:1 PC, on a western diet with similar deficits in 16:0, 20:4 PC and 18:0, 20:4 PC as observed on a chow diet

• additional reductions in 16:1, 18:2 PC and 18:1, 20:4 PC in western diet-fed livers

• severe reductions of phosphatidlyethanolamine (PE) species containing arachidonate chains on both chow and western diets

• highly selective reductions in 16:0, 20:4 PC and 18:0, 20:4 PC in plasma VLDL fractions on a chow diet, suggesting that phospholipid deficits of liver membranes are passed on to the VLDL particles that they generate

• severe loss of arachidonate in liver on a chow diet is observed in phospholipids (PLs), but not in TGs or in cholesterol esters

• total level of PC is not significantly altered in liver under either diet

decreased circulating VLDL phospholipid level ( J:220827 )

• highly selective reductions in 16:0, 20:4 PC and 18:0, 20:4 PC in plasma VLDL fractions on a chow diet, suggesting that phospholipid deficits of liver membranes are passed on to the VLDL particles that they generate

increased liver triglyceride level ( J:220827 )

• trend towards increased TG stores in the liver following an overnight fast

• prominent accumulation of hepatic TGs following a western diet for 9 weeks

• accumulation of hepatic TGs following a high-sucrose diet for 3 weeks

liver/biliary system

increased liver cholesterol level ( J:220827 )

• prominent accumulation of hepatic cholesterol following a western diet for 9 weeks

• increase in total cholesterol ester and a number of cholesterol ester species on a chow diet, with generally similar results on a western diet

increased liver triglyceride level ( J:220827 )

• trend towards increased TG stores in the liver following an overnight fast

• prominent accumulation of hepatic TGs following a western diet for 9 weeks

• accumulation of hepatic TGs following a high-sucrose diet for 3 weeks

hepatic steatosis ( J:220827 )

• histological evidence of increased lipid accumulation in the liver on a chow diet

Genotype
MGI:5003273

cn182

• Allelic Composition: Cul4a^tm1.1Pra/Cul4a^tm1.1Pra; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6NTac * DBA

liver/biliary system

decreased hepatocyte proliferation ( J:172043 )

• following CCl4 injury

growth/size/body

decreased body weight ( J:172043 )

homeostasis/metabolism

increased susceptibility to injury ( J:172043 )

• following CCl4 injury, mice exhibit decreased hepatocyte proliferation compared with control mice

cellular

decreased hepatocyte proliferation ( J:172043 )

• following CCl4 injury

Genotype
MGI:4820736

cn183

• Allelic Composition: Psmg1^tm1.1Smta/Psmg1^tm1.1Smta; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * CBA * DBA

mortality/aging

mortality/aging ( J:162790 )

N • mortality is normal through 18 months

liver/biliary system

abnormal liver sinusoid morphology ( J:162790 )

• narrow sinusoids

abnormal hepatic cord morphology ( J:162790 )

• irregular hepatic cords

abnormal hepatocyte morphology ( J:162790 )

• mice exhibit enlarged hepatocytes with irregular hepatic cords and narrow sinusoids compared to in wild-type mice

• hepatocytes exhibit aberrant proliferation of the peroxisomes compared with wild-type cells

abnormal hepatocyte physiology ( J:162790 )

• hepatocytes undergo premature senescence compared with wild-type cells

cardiovascular system

abnormal liver sinusoid morphology ( J:162790 )

• narrow sinusoids

Genotype
MGI:4422187

cn184

• Allelic Composition: Stk3^tm1.1Yy/Stk3^tm1Yy; Stk4^tm1.1Yy/Stk4^tm1.1Yy; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * CBA * DBA

liver/biliary system

increased hepatocyte apoptosis ( J:156541 )

• slight

increased hepatocyte proliferation ( J:156541 )

abnormal liver morphology ( J:156541 )

• dysplasia at 1 month of age

• increase in hepatocyte cell density

enlarged liver ( J:156541 )

• at 1 month of age

abnormal hepatocyte morphology ( J:156541 )

• smaller

• some cells have vacuolated cytoplasm

cellular

increased hepatocyte apoptosis ( J:156541 )

• slight

increased hepatocyte proliferation ( J:156541 )

growth/size/body

enlarged liver ( J:156541 )

• at 1 month of age

Genotype
MGI:6739868

cn185

• Allelic Composition: Ppdpf^tm1Nju/Ppdpf^tm1Nju; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

growth/size/body

increased body weight ( J:307283 )

• mice exhibit a higher body weight than wild-type mice at 8 months of age

increased liver weight ( J:307283 )

• livers are heavier at 8 months of age

• mice fed a high-fat diet exhibit a greater increase in liver weight than wild-type mice

homeostasis/metabolism

increased circulating free fatty acids level ( J:307283 )

• nonesterified fatty acid (NEFA) levels are increased

• mice fed a high-fat diet exhibit a greater increase in NEFA levels than wild-type mice

increased circulating triglyceride level ( J:307283 )

• serum triglycerides are increased

• mice fed a high-fat diet show a greater increase in serum triglyceride levels than wild-type mice

impaired glucose tolerance ( J:307283 )

• mice develop more severe glucose intolerance than wild-type mice after 16 weeks of a high-fat diet

insulin resistance ( J:307283 )

• mice develop more severe insulin resistance than wild-type mice after 16 weeks of a high-fat diet

increased liver triglyceride level ( J:307283 )

• liver triglyceride levels are increased

• mice fed a high-fat diet show a greater increase in liver triglyceride levels than wild-type mice

increased lipogenesis ( J:307283 )

• primary hepatocytes treated with palmitic acid to induce steatosis in vitro show a greater increase in lipid deposition than in wild-type hepatocytes

• hepatocytes treated with mTOR inhibitor Torin1 show reduced lipid deposition

liver/biliary system

increased liver weight ( J:307283 )

• livers are heavier at 8 months of age

• mice fed a high-fat diet exhibit a greater increase in liver weight than wild-type mice

increased liver triglyceride level ( J:307283 )

• liver triglyceride levels are increased

• mice fed a high-fat diet show a greater increase in liver triglyceride levels than wild-type mice

hepatic steatosis ( J:307283 )

• mice develop fatty liver disease, with livers showing lipid droplets with increased size and serious steatosis at 8 months of age

• mice treated with the mTOR inhibitor Rapamycin show reduced body weight, liver weight, liver triglyceride, liver NEFA, inhibition of lipid droplet formation

increased susceptibility to diet-induced hepatic steatosis ( J:307283 )

• mice exhibit increased susceptibility to high-fat diet-induced non-alcoholic fatty liver disease, with mice showing a greater increase in liver weight, liver triglyceride and NEFA content, more serious steatosis and higher serum triglyceride levels, develop more severe glucose intolerance and insulin resistance, and have larger and more lipid droplets in the livers

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
metabolic dysfunction-associated steatotic liver disease		DOID:0080208	OMIM:613282 OMIM:613387	J:307283

Genotype
MGI:4415291

cn186

• Allelic Composition: Pcyt2^tm1.1Suja/Pcyt2^tm1.1Suja; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

Pcyt2^tm1.1Suja/Pcyt2^tm1.1Suja Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 liver with hepatocytes engorged with lipid droplets

homeostasis/metabolism

decreased circulating triglyceride level ( J:155630 )

increased liver cholesterol level ( J:155630 )

• 2-fold

increased liver triglyceride level ( J:155630 )

• 10-fold

liver/biliary system

increased liver cholesterol level ( J:155630 )

• 2-fold

increased liver triglyceride level ( J:155630 )

• 10-fold

hepatic steatosis ( J:155630 )

pale liver ( J:155630 )

Genotype
MGI:6515758

cn187

• Allelic Composition: Polr2m^tm1.1Rgr/Polr2m^tm1.1Rgr; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:291184 )

N • liver weights are similar to controls

increased hepatocyte karyomegaly ( J:291184 )

• large cells with enlarged nuclei are seen

abnormal hepatocyte physiology ( J:291184 )

• expression analysis indicates more cells have re-entered the cell cycle but that the cell cycle appears to arrest

homeostasis/metabolism

decreased circulating triglyceride level ( J:291184 )

increased circulating alkaline phosphatase level ( J:291184 )

cellular

increased hepatocyte karyomegaly ( J:291184 )

• large cells with enlarged nuclei are seen

Genotype
MGI:7407341

cn188

• Allelic Composition: Cpt2^tm1Mwol/Cpt2^tm1Mwol; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased circulating ketone body level ( J:348980 )

• decrease in fasting ketone bodies

increased circulating cholesterol level ( J:348980 )

• in fasted mice

increased circulating triglyceride level ( J:348980 )

• in fasted mice

increased liver triglyceride level ( J:348980 )

• in fasted mice

liver/biliary system

enlarged liver ( J:348980 )

• larger and paler in fasted mice

increased liver triglyceride level ( J:348980 )

• in fasted mice

abnormal hepatocyte morphology ( J:348980 )

• in fasted mice hepatocytes appear swollen and lipid laden

hepatic steatosis ( J:348980 )

• fasting induced lipid accumulation

pale liver ( J:348980 )

• in fasted mice

growth/size/body

enlarged liver ( J:348980 )

• larger and paler in fasted mice

Genotype
MGI:6393588

cn189

• Allelic Composition: Mir100^em1Nju/Mir100^em1Nju; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

increased hepatocyte karyomegaly ( J:281439 )

• in aged mice

liver inflammation ( J:281439 )

• in aged mice

homeostasis/metabolism

increased circulating alanine transaminase level ( J:281439 )

• in aged mice

increased circulating aspartate transaminase level ( J:281439 )

• in aged mice

immune system

liver inflammation ( J:281439 )

• in aged mice

cellular

increased hepatocyte karyomegaly ( J:281439 )

• in aged mice

Genotype
MGI:6361915

cn190

• Allelic Composition: Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(CAG-Dusp26)#Jhxia/0
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:279111 )

• in mice fed a high-fat diet

increased circulating alanine transaminase level ( J:279111 )

• in mice fed a high-fat diet, but not as severe as in control mice

increased circulating aspartate transaminase level ( J:279111 )

• in mice fed a high-fat diet, but not as severe as in control mice

impaired glucose tolerance ( J:279111 )

• in mice fed a high-fat diet

insulin resistance ( J:279111 )

• mice fed a high-fat diet do not exhibit as severe insulin resistance as in control mice

decreased liver cholesterol level ( J:279111 )

• in mice fed a high-fat diet

decreased liver free fatty acids level ( J:279111 )

• in mice fed a high-fat diet

decreased liver triglyceride level ( J:279111 )

• in mice fed a high-fat diet

liver/biliary system

decreased liver cholesterol level ( J:279111 )

• in mice fed a high-fat diet

decreased liver free fatty acids level ( J:279111 )

• in mice fed a high-fat diet

decreased liver triglyceride level ( J:279111 )

• in mice fed a high-fat diet

decreased liver weight ( J:279111 )

• in mice fed a high-fat diet

decreased susceptibility to diet-induced hepatic steatosis ( J:279111 )

• in mice fed a high-fat diet

growth/size/body

decreased susceptibility to diet-induced obesity ( J:279111 )

• in mice fed a high-fat diet

Genotype
MGI:6361914

cn191

• Allelic Composition: Dusp26^em1Jhxia/Dusp26^em1Jhxia; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

increased circulating glucose level ( J:279111 )

• more so than controls in mice fed a high-fat diet

increased fasting circulating glucose level ( J:279111 )

• in mice fed a high-fat and high-cholesterol diet

increased circulating alanine transaminase level ( J:279111 )

• in mice fed a high-fat diet

increased circulating aspartate transaminase level ( J:279111 )

• in mice fed a high-fat diet

impaired glucose tolerance ( J:279111 )

• more so than controls in mice fed a high-fat diet

• in mice fed a high-fat and high-cholesterol diet

decreased liver glycogen level ( J:279111 )

• in mice fed a high-fat diet

insulin resistance ( J:279111 )

• more so than controls in mice fed a high-fat diet

increased liver cholesterol level ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

increased liver free fatty acids level ( J:279111 )

• in mice fed a high-fat diet

increased liver triglyceride level ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

liver/biliary system

abnormal liver morphology ( J:279111 )

• increased susceptibility to hepatic steatosis in mice fed a high-fat diet or a high-fat and high-cholesterol diet

increased liver weight ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

decreased liver glycogen level ( J:279111 )

• in mice fed a high-fat diet

increased liver cholesterol level ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

increased liver free fatty acids level ( J:279111 )

• in mice fed a high-fat diet

increased liver triglyceride level ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

liver fibrosis ( J:279111 )

• in mice fed a high-fat and high-cholesterol diet

growth/size/body

increased susceptibility to diet-induced obesity ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

increased liver weight ( J:279111 )

• in mice fed a high-fat diet or a high-fat and high-cholesterol diet

Genotype
MGI:3828255

cn192

• Allelic Composition: Nfe2l1^tm1Mym/Nfe2l1^tm1Mym; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

hepatic steatosis ( J:143468 )

• by 8 weeks, livers accumulate many lipid-containing vacuoles unlike in wild-type livers

homeostasis/metabolism

increased circulating alanine transaminase level ( J:143468 )

• at 8 weeks

increased circulating aspartate transaminase level ( J:143468 )

• at 8 weeks

Genotype
MGI:6359866

cn193

• Allelic Composition: Mirc53^tm1.1Gning/Mirc53^tm1.1Gning; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased susceptibility to injury ( J:278082 )

• mice treated with methionine and choline deficient diet (MCDD) or chronic carbon tetrachloride (CCl4) exhibit reduced hepatic steatosis, fibrosis, and inflammatory infiltration with less severe increase in serum alanine transferase levels compared with wild-type mice

Genotype
MGI:3809845

cn194

• Allelic Composition: Txnip^tm1Road/Txnip^tm1Road; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

mortality/aging

mortality/aging ( J:132756 )

N • mice exhibit normal viability

reproductive system

reproductive system phenotype ( J:132756 )

N • mice exhibit normal reproduction

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:132756 )

N • mice exhibit normal serum triglyceride, ketone and glucose levels

growth/size/body

growth/size/body region phenotype ( J:132756 )

N • mice exhibit normal growth

Genotype
MGI:4457494

cn195

• Allelic Composition: Por^tm3Ding/Por^tm3Ding; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

mortality/aging

mortality/aging ( J:159168 )

N • mice exhibit normal embryonic survival

reproductive system

female infertility ( J:159168 )

♀

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:159168 )

N • mice exhibit normal circulating cholesterol levels

increased circulating testosterone level ( J:159168 )

increased circulating progesterone level ( J:159168 )

abnormal enzyme/coenzyme activity ( J:159168 )

• NNK-treated mice exhibit reduced levels of DNA adduction (a measure of NKK activation) compared with similarly treated wild-type mice

behavior/neurological

behavior/neurological phenotype ( J:159168 )

N • mice exhibit normal sleeping time in response to pentobarbital treatment

growth/size/body

growth/size/body region phenotype ( J:159168 )

N • mice exhibit normal body and organ weights

Genotype
MGI:7610684

cn196

• Allelic Composition: Gpcpd1^{tm1c(EUCOMM)Hmgu}/Gpcpd1^{tm1c(EUCOMM)Hmgu}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:345630 )

♂N • do not show glucose intolerance at 12 weeks of age

Genotype
MGI:4457497

cn197

• Allelic Composition: Sav1^tm2.1Dlim/Sav1^tm2.1Dlim; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:160325 )

N • liver function is normal and liver regeneration

abnormal liver morphology ( J:160325 )

• mice exhibit regions of abnormal morphology with irregular and enlarged hepatocytes unlike wild-type mice

• however, gross hepatic architecture is normal

enlarged liver ( J:160325 )

• in mice fed a diet supplemented with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC) for 6 weeks

increased liver weight ( J:160325 )

• in mice fed a diet supplemented with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC)

abnormal hepatocyte morphology ( J:160325 )

• mice exhibit regions of abnormal morphology with irregular and enlarged hepatocytes unlike wild-type mice

• however, mice exhibit normal maturation and differentiation of hepatocytes

abnormal portal lobule morphology ( J:160325 )

• mice fed a diet supplemented with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC) for 2 to 4 weeks exhibit changes in the portal tract region unlike similarly treated wild-type mice

increased hepatocellular carcinoma incidence ( J:238319 )

• mice develop hepatocellular carcinoma; tumors show abundant feeding arteries but no portal venous perfusion

increased hepatoma incidence ( J:160325 )

• by 12 months of age

abnormal oval cell morphology ( J:160325 )

• by 6 months, mice exhibit an increase in the number of immature progenitor or oval-like cells in the liver compared with wild-type mice

• mice fed a diet supplemented with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC) exhibit an increase in oval cells compared with similarly treated wild-type mice

abnormal oval cell physiology ( J:160325 )

• at 3 to 12 months, more proliferating oval cells are observed than in wild-type mice

• mice fed a diet supplemented with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC) exhibit an increase in proliferating oval cells compared with similarly treated wild-type mice

• oval cells from mice fed a diet supplemented with DCC exhibit increased proliferative capacity compared with cells isolated from similarly treated wild-type mice

neoplasm

increased hepatocellular carcinoma incidence ( J:238319 )

• mice develop hepatocellular carcinoma; tumors show abundant feeding arteries but no portal venous perfusion

increased hepatoma incidence ( J:160325 )

• by 12 months of age

growth/size/body

enlarged liver ( J:160325 )

• in mice fed a diet supplemented with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC) for 6 weeks

increased liver weight ( J:160325 )

• in mice fed a diet supplemented with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:238319

Genotype
MGI:4882058

cn198

• Allelic Composition: Pnpt1^tm1Teit/Pnpt1^tm1Teit; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

cellular

abnormal mitochondrial crista morphology ( J:167932 )

• mitochondria in liver cells exhibit disordered circular and smooth IM cristae compared to in wild-type cells

abnormal mitochondrial physiology ( J:167932 )

• mitochondria in liver cells exhibit inefficient mtRNA precursor processing and impaired RNA import compared to in wild-type cells

abnormal mitochondrial ATP synthesis coupled electron transport ( J:167932 )

• mitochondria in liver cells exhibit a 1.5- to 2-fold decrease in activity of Complex IV and Complexes II+III+IV compared to in wild-type cells

Genotype
MGI:4947224

cn199

• Allelic Composition: Derl2^tm1.1Hpl/Derl2^tm1.1Hpl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:170650 )

N • liver function is normal

Genotype
MGI:4950282

cn200

• Allelic Composition: Ccl2^tm1.1Pame/Ccl2^tm1.1Pame; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

immune system

immune system phenotype ( J:171379 )

N • LPS-induced monocyte emigration is normal

Genotype
MGI:5295292

cn201

• Allelic Composition: Fbxl5^tm2.1Kei/Fbxl5^tm2.1Kei; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

cellular

abnormal hepatocyte mitochondrial morphology ( J:176655 )

• mitochondriopathy associated with small lipid droplets

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:176655 )

• most mice die within 1 day of being placed on a high iron diet

• mice that survive more than 1 day on a high iron diet consume very little of the diet and die of starvation within 2 weeks

homeostasis/metabolism

increased circulating iron level ( J:176655 )

abnormal circulating enzyme level ( J:176655 )

increased circulating alanine transaminase level ( J:176655 )

• serum levels are elevated about 100 fold in mice on a high iron diet

increased circulating aspartate transaminase level ( J:176655 )

• serum levels are elevated about 100 fold in mice on a high iron diet

increased circulating lactate dehydrogenase level ( J:176655 )

• serum levels are elevated about 100 fold in mice on a high iron diet

decreased circulating unsaturated transferrin level ( J:176655 )

• elevated transferrin saturation

abnormal blood coagulation ( J:176655 )

increased partial thromboplastin time ( J:176655 )

• activated partial thromboplastin time issignificantly increased in mice on a high iron diet suggestive of a severe coagulopathy

increased prothrombin time ( J:176655 )

• prothrombin time is significantly increased in mice on a high iron diet suggestive of a severe coagulopathy

increased liver iron level ( J:176655 )

• accumulation of ferrous iron in hepatocytes

cardiovascular system

liver hemorrhage ( J:176655 )

• in mice on a high iron diet

liver/biliary system

increased liver iron level ( J:176655 )

• accumulation of ferrous iron in hepatocytes

abnormal hepatocyte morphology ( J:176655 )

• the cytoplasm is only weakly eosinophilic and contains numerous microvesicular vacuoles

• deposition of multiple small lipid droplets with an undisplaced nucleus are seen in liver cells

abnormal hepatocyte mitochondrial morphology ( J:176655 )

• mitochondriopathy associated with small lipid droplets

hepatic steatosis ( J:176655 )

• in mice on a high iron diet for 1 day

pale liver ( J:176655 )

abnormal liver physiology ( J:176655 )

liver hemorrhage ( J:176655 )

• in mice on a high iron diet

liver inflammation ( J:176655 )

• lobular infiltration of inflammatory cells (e.g. lymphocytes and neutrophils) indicating mild inflammation

liver failure ( J:176655 )

• elevation of hepatic and biliary tract enzymes in mice on a high iron diet is suggestive of acute progressive destruction of hepatocytes

• massive cell death, predominantly in the area around portal veins is seen in mice on a high iron diet

• addition of the antioxidant N-acetyl-L-cysteine to the water attenuates cell death in mice on a high iron diet

immune system

liver inflammation ( J:176655 )

• lobular infiltration of inflammatory cells (e.g. lymphocytes and neutrophils) indicating mild inflammation

Genotype
MGI:5437229

cn202

• Allelic Composition: Cdo1^tm1Mhst/Cdo1^tm1Mhst; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

abnormal homeostasis ( J:186922 )

• reduced kidney and pancreas hypotaurine

decreased cysteine level ( J:186922 )

• reduced liver cysteine

abnormal blood homeostasis ( J:186922 )

• reduced plasma hypotaurine and cysteine

decreased circulating cysteine level ( J:186922 )

• reduced plasma cysteine

Genotype
MGI:7858939

cn203

• Allelic Composition: Sptlc3^em1Cowl/Sptlc3^em1Cowl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:361357 )

N • no apparent differences in steatosis, hepatomegaly, liver triglyceride levels, liver glycogen levels, or markers of inflammation when fed a high fat diet compared to diet matched controls

abnormal hepatocyte physiology ( J:361357 )

• primary hepatocytes cultured in glucose free medium accumulate only 50 uM glucose in the medium compared to ~125 uM for controls

• expression of genes related to gluconeogenesis is low in primary hepatocytes related to controls and fails to increase in response to glucagon treatment

• labeled-metabolite analysis indicates that the impairment is primarily due to suppressed conversion of oxalacetate to PEP and downstream metabolites

• glucagon induced increase in cAMP levels is impaired and addition of a cell permeable cAMP derivative increases expression of gluconeogenesis related genes

homeostasis/metabolism

decreased fasting circulating glucose level ( J:361357 )

♂ • on a high-fat diet mice do not display the expected increase in fasting glucose levels seen in diet matched controls

impaired gluconeogenesis ( J:361357 )

• primary hepatocytes cultured in glucose free medium accumulate only 50 uM glucose in the medium compared to ~125 uM for controls

• expression of genes related to gluconeogenesis is low in primary hepatocytes related to controls and fails to increase in response to glucagon treatment

• labeled-metabolite analysis indicates that the impairment is primarily due to suppressed conversion of oxalacetate to PEP and downstream metabolites

improved glucose tolerance ( J:361357 )

♂ • in mice on a high-fat diet compared to diet matched controls

decreased susceptibility to diet-induced non-insulin dependent diabetes ( J:361357 )

♂ • glucose tolerance test indicate a partial protection from high-fat diet induced diabetes

♂ • however, high-fat diet induced increase in postprandial insulin levels is similar to diet matched controls

Genotype
MGI:5466370

cn204

• Allelic Composition: Selenop^tm3.1Rfb/Selenop^tm3.1Rfb; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

Curling and splaying of hind limbs in Selenop^tm3.1Rfb/Selenop^tm3.1Rfb Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice fed a selenium-deficient diet

reproductive system

oligozoospermia ( J:192636 )

♂ • in mice fed a selenium-deficient diet

teratozoospermia ( J:192636 )

♂ • kinked spermatozoa in mice fed a selenium-deficient diet

homeostasis/metabolism

abnormal selenium level ( J:192636 )

• mice fed a selenium-adequate diet supplemented with selenium exhibit increased liver selenium incorporation and decreased whole body, liver, kidney, brain, testis and muscle compared with control mice

• mice fed a selenium-deficient diet exhibit increased liver selenium levels and decreased kidney, brain, testis, muscle and whole body levels compared with control mice

increased urine selenium level ( J:192636 )

• more than doubled in mice fed a selenium-adequate diet supplemented with selenium

behavior/neurological

limb grasping ( J:192636 )

• beginning at 16 weeks in mice fed a selenium-deficient diet

abnormal gait ( J:192636 )

• wide-based gait in hind limbs beginning at 22 weeks in mice fed a selenium-deficient diet

growth/size/body

decreased body weight ( J:192636 )

• mice fed a selenium-deficient diet cease to gain weight after 12 weeks unlike control mice

renal/urinary system

increased urine selenium level ( J:192636 )

• more than doubled in mice fed a selenium-adequate diet supplemented with selenium

cellular

oligozoospermia ( J:192636 )

♂ • in mice fed a selenium-deficient diet

teratozoospermia ( J:192636 )

♂ • kinked spermatozoa in mice fed a selenium-deficient diet

Genotype
MGI:5487467

cn205

• Allelic Composition: Sqstm1^tm2.1Jmos/Sqstm1^tm2.1Jmos; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

growth/size/body

growth/size/body region phenotype ( J:194291 )

N • mice fed standard chow or a high fat diet exhibit normal body weight and composition

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:194291 )

N • mice fed standard chow or a high fat diet exhibit normal glucose tolerance

liver/biliary system

liver/biliary system phenotype ( J:194291 )

N • mice do not exhibit liver steatosis

behavior/neurological

behavior/neurological phenotype ( J:194291 )

N • mice fed standard chow or a high fat diet exhibit normal food intake

Genotype
MGI:6196883

cn206

• Allelic Composition: Creg1^em1Yal/Creg1^em1Yal; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

abnormal circulating enzyme level ( J:263073 )

increased circulating alanine transaminase level ( J:263073 )

• when fed a high fat diet

increased circulating alkaline phosphatase level ( J:263073 )

• when fed a high fat diet

increased circulating aspartate transaminase level ( J:263073 )

• when fed a high fat diet

abnormal glucose homeostasis ( J:263073 )

increased fasting circulating glucose level ( J:263073 )

• when fed a high fat diet

increased circulating insulin level ( J:263073 )

• fasted levels when mice are fed a high fat diet

impaired glucose tolerance ( J:263073 )

• when fed a high fat diet

decreased glycogen level ( J:263073 )

• when fed a high fat diet

insulin resistance ( J:263073 )

• when fed a high fat diet

abnormal lipid homeostasis ( J:263073 )

increased liver cholesterol level ( J:263073 )

• when fed a high fat diet

increased liver free fatty acids level ( J:263073 )

• nonesterified when fed a high fat diet

liver/biliary system

increased liver weight ( J:263073 )

• when fed a high fat diet

increased liver cholesterol level ( J:263073 )

• when fed a high fat diet

increased liver free fatty acids level ( J:263073 )

• nonesterified when fed a high fat diet

decreased susceptibility to diet-induced hepatic steatosis ( J:263073 )

• when fed a high fat diet

growth/size/body

increased body weight ( J:263073 )

• when fed a high fat diet

increased liver weight ( J:263073 )

• when fed a high fat diet

Genotype
MGI:6108884

cn207

• Allelic Composition: Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Trmu^tm1Tomik/Trmu^tm1Tomik
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:235644 )

N • glutathione level in liver

N • cysteine level in liver

N • lactate dehydrogenase level in 16-week old mice

abnormal homeostasis ( J:235644 )

• in serum of 3-week old mice

decreased circulating creatinine level ( J:235644 )

increased circulating lactate level ( J:235644 )

decreased circulating cholesterol level ( J:235644 )

decreased circulating HDL cholesterol level ( J:235644 )

decreased circulating calcium level ( J:235644 )

increased circulating alanine transaminase level ( J:235644 )

• in serum of 3-week old and 16-week old mice

decreased circulating amylase level ( J:235644 )

increased circulating aspartate transaminase level ( J:235644 )

• in serum of 3-week old and 16-week old mice

increased circulating lactate dehydrogenase level ( J:235644 )

decreased circulating serum albumin level ( J:235644 )

abnormal nucleotide metabolism ( J:235644 )

• in hepatocytes

• absence of s2U (2-thiouridine) modification of mitochondrial Glu-, Gln- and Lys-tRNAs

• tau-m5U (5-taurinomethyluridine) modification of mitochondrial Glu-, Gln- and Lys-tRNAs

• increased mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine) modification of cytosolic tRNAs

• increased ms2i6A (2-methylthio-N6-isopentenyladenosine) modification of mitochondrial tRNAs

cellular

increased cell nucleus count ( J:235644 )

• in hepatocytes

increased hepatocyte karyomegaly ( J:235644 )

• in 3-week old and 16-week old mice

abnormal hepatocyte mitochondrial morphology ( J:235644 )

• inner vacuole with multiple membrane layers in some hepatocytes

• very low electron density (in electron microscopy) in some hepatocytes

increased mitochondrial DNA content ( J:235644 )

• up-regulated mt-DNA copy number (relative to nuclear) in 16-week old mice

abnormal mitochondrial crista morphology ( J:235644 )

• abnormally swollen or absent cristae

increased mitochondrial size ( J:235644 )

• mitochondrial area 4.3-fold larger in hepatocytes

abnormal mitochondrial physiology ( J:235644 )

• reduced translation of proteins larger than 25 kDa in hepatocytes

• slightly increased translation of proteins smaller than 25 kDa in hepatocytes

• impaired formation and/or activity of respiratory complexes I, III and IV in hepatocytes

abnormal tricarboxylic acid cycle ( J:235644 )

• significant increase of citrate synthase activity in liver

liver/biliary system

increased hepatocyte karyomegaly ( J:235644 )

• in 3-week old and 16-week old mice

abnormal hepatocyte mitochondrial morphology ( J:235644 )

• inner vacuole with multiple membrane layers in some hepatocytes

• very low electron density (in electron microscopy) in some hepatocytes

hepatic necrosis ( J:235644 )

• spotty necrosis in 3-week old and 16-week old mice

immune system

abnormal inflammatory response ( J:235644 )

• infiltration of macrophages in the liver of 3-week old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
liver disease		DOID:409		J:235644

Genotype
MGI:3618231

cn208

• Allelic Composition: Gck^tm1Hrt/Gck⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

cardiovascular system

cardiac fibrosis ( J:250069 )

• mice exhibit cardiac fibrosis, showing increased levels of myocardial collagen which is broken and arranged in a disordered collagen fiber network around the myocardial cells

• treatment with insulin or rosiglitazone decreases collagen and glycoprotein content in the heart

abnormal heart echocardiography feature ( J:250069 )

• echocardiography indicates decreased left ventricle internal dimension during diastole and systole and increased left ventricle posterior wall thickness during diastole and systole in 60 week old mice

• left ventricle internal dimension during diastole is increased after treatment with insulin or rosiglitazone

prolonged PR interval ( J:250069 )

• 60 week old mice exhibit longer PR intervals

• treatment with insulin or rosiglitazone shortens the PR interval

prolonged QRS complex duration ( J:250069 )

• 60 week old mice exhibit longer QRS intervals

• treatment with insulin or rosiglitazone shortens the QRS interval

• however, changes in heart rates, P duration, QT intervals, and corrected QT intervals are not different from wild-type mice

homeostasis/metabolism

increased circulating glucose level ( J:105247 )

• from 2 weeks of age, mice showed increasing blood glucose levels in an age-dependent manner (from 3.8 mmol/L at 2 weeks to 8.9 mmol/L at 6 weeks); level at 6 weeks is significantly higher than control level (5.3 mmol/L)

increased fasting circulating glucose level ( J:250069 )

• fasting glucose levels are increased

• treatment with rosiglitazone does not change fasting glucose levels

impaired glucose tolerance ( J:105247 , J:250069 )

• mice display glucose intolerance (J:105247)

• glucose levels at 0, 30, 60, and 120 minutes after glucose injection are higher (J:250069)

• treatment with rosiglitazone decreases the impairment in the glucose tolerance response at the 60 and 120 minute time points (J:250069)

insulin resistance ( J:250069 )

• homeostasis model assessment of insulin resistance (HOMA-IR) levels are increased

• treatment with rosiglitazone results in a decrease in HOMA-IR levels

cellular

abnormal mitochondrial crista morphology ( J:250069 )

• cristae density of the mitochondria is decreased in the myocardium

increased mitochondrial number ( J:250069 )

• mitochondrial volume density and number are increased in the myocardium

• treatment with insulin or rosiglitazone restores these properties to normal levels

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:250069 )

• the homeostasis model assessment of beta-cell function (HOMA-Beta-cell) levels are decreased

• treatment with rosiglitazone does not change HOMA-Beta-cell levels

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young type 2		DOID:0111100	OMIM:125851	J:105247 , J:250069

Genotype
MGI:5912276

cn209

• Allelic Composition: Smarcd1^tm1.1Jddl/Smarcd1^tm1.1Jddl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased intestinal cholesterol absorption ( J:228944 )

decreased circulating cholesterol level ( J:228944 )

• partially resistant to Western diet-induced hypercholesterolemia despite similar weight gain compared to controls

• total plasma cholesterol concentration on a Western diet is approximately 40% lower compared to controls

• however, levels in mice on a standard chow diet are similar to controls

decreased circulating HDL cholesterol level ( J:228944 )

• in mice on a Western diet

decreased circulating LDL cholesterol level ( J:228944 )

• in mice on a Western diet

decreased circulating VLDL cholesterol level ( J:228944 )

• in mice on a Western diet

decreased circulating alanine transaminase level ( J:228944 )

decreased circulating aspartate transaminase level ( J:228944 )

decreased bile salt level ( J:228944 )

• 37% decrease in total bile volume and biliary acid content

• the liver/gallbladder and intestine bile acid pool sizes are both significantly decreased

increased cholesterol level ( J:228944 )

• cholesterol excretion in feces is significantly increased

increased feces cholesterol level ( J:228944 )

• cholesterol excretion in feces is significantly increased

increased liver cholesterol level ( J:228944 )

digestive/alimentary system

increased feces cholesterol level ( J:228944 )

• cholesterol excretion in feces is significantly increased

decreased intestinal cholesterol absorption ( J:228944 )

liver/biliary system

increased liver cholesterol level ( J:228944 )

Genotype
MGI:5588662

cn210

• Allelic Composition: Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tspo^tm1.1Maf/Tspo^tm1.1Maf
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

liver/biliary system phenotype ( J:214129 )

N • mice show normal liver morphology and liver mitochondria morphology and function

Genotype
MGI:5882068

cn211

• Allelic Composition: Klf14^tm1.1Yec/Klf14^tm1.1Yec; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased circulating HDL cholesterol level ( J:226403 )

Genotype
MGI:5825445

cn212

• Allelic Composition: Trnau1ap^tm2.1Usch/Trnau1ap^tm2.1Usch; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:237714 )

N • mice exhibit normal serum transaminase and selenium levels

Genotype
MGI:8210455

cn213

• Allelic Composition: Rab30^em1Mwol/Rab30^em1Mwol; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

growth/size/body

increased body weight ( J:348980 )

♂ • males are larger by 1.77g compared to controls

liver/biliary system

liver/biliary system phenotype ( J:348980 )

N • no change in liver triglycerides or lipid levels in the fasted state

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:348980 )

N • no significant differences in serum metabolites unlike in whole body knockout mice

increased circulating glucose level ( J:348980 )

♀ • increased fasted blood glucose

Genotype
MGI:8210461

cn214

• Allelic Composition: Cpt2^tm1Mwol/Cpt2^tm1Mwol; Rab30^em1Mwol/Rab30^em1Mwol; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:348980 )

N • unlike in fasted mice with liver specific loss of Cpt2 alone, double knockout mice have a reversal of the increase in triglycerides and cholesterol levels back to control levels

decreased circulating glucose level ( J:348980 )

♀ • in fasted females compared to controls

decreased circulating ketone body level ( J:348980 )

• decrease in fasting ketone bodies

increased circulating free fatty acids level ( J:348980 )

• compared to fasted controls and fasted mice with hepatic specific loss of Cpt2 only

• differences are not seen in the fed state

increased liver triglyceride level ( J:348980 )

liver/biliary system

enlarged liver ( J:348980 )

• larger and paler in fasted mice

increased liver triglyceride level ( J:348980 )

abnormal hepatocyte morphology ( J:348980 )

• in fasted mice hepatocytes appear swollen and lipid laden

hepatic steatosis ( J:348980 )

• fasting induced lipid accumulation

pale liver ( J:348980 )

• in fasted mice

growth/size/body

enlarged liver ( J:348980 )

• larger and paler in fasted mice

Genotype
MGI:5781097

cn215

• Allelic Composition: Ddit3^tm1.1Irt/Ddit3^tm1.1Irt; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(Mup3-Plau)350-2Eps/?
• Genetic Background: involves: C57BL/6 * DBA

liver/biliary system

increased hepatocellular carcinoma incidence ( J:233146 )

• mice fed a high fat diet develop hepatocellular carcinoma and show increased tumor multiplicity without affecting tumor size compared to single Tg(Mup3-Plau)350-2Eps transgenic mice

neoplasm

increased hepatocellular carcinoma incidence ( J:233146 )

• mice fed a high fat diet develop hepatocellular carcinoma and show increased tumor multiplicity without affecting tumor size compared to single Tg(Mup3-Plau)350-2Eps transgenic mice

Genotype
MGI:5770122

cn216

• Allelic Composition: Dio3^tm1Dmst/Dio3^tm1Dmst; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

growth/size/body

growth/size/body region phenotype ( J:218350 )

♂N • at 8-10 weeks of age, mice exhibit normal body weight relative to control mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:218350 )

♂N • at 8-10 weeks of age, baseline serum thyroxine and triiodothyronine concentrations are normal and serum TSH is not suppressed relative to control mice, indicating normal thyroid status in the well state

♂N • serum total protein concentrations are also normal

increased circulating thyroxine level ( J:218350 )

♂ • mice exhibit an 81% increase in serum T4 levels between 24 and 48 hrs post CCl4 injection, unlike control mice where serum T4 levels remain suppressed

♂ • comparisons between 0 and 48 hrs post CCl4 injection confirm that serum T4 levels return to near pre-injury levels, unlike in control mice

increased circulating triiodothyronine level ( J:218350 )

♂ • mice exhibit a 76% increase in serum T3 levels between 24 and 48 hrs post CCl4 injection, unlike control mice where serum T3 levels remain suppressed

♂ • comparisons between 0 and 48 hrs post CCl4 injection confirm that serum T4 levels return to near pre-injury levels, unlike in control mice

abnormal response to injury ( J:218350 )

♂ • mice display accelerated recovery from CCl4-induced hypothyroxinemia and hypotriiodothyronemia

liver/biliary system

liver/biliary system phenotype ( J:218350 )

♂N • at 8-10 weeks of age, mice exhibit normal liver weight and histology relative to control mice

♂N • following CCl4-induced hepatonecrosis, mice exhibit normal injury tolerance and intact liver regeneration with complete normalization of liver histology at 120 hrs post CCl4 injection, indicating normal local responses to liver injury

increased hepatocyte proliferation ( J:218350 )

♂ • following CCl4-induced hepatonecrosis, mice exhibit higher expression of proliferating cell markers (PCNA, cyclins A2 and E1) at 48 hrs post CCl4 injection relative to control mice

cellular

increased hepatocyte proliferation ( J:218350 )

♂ • following CCl4-induced hepatonecrosis, mice exhibit higher expression of proliferating cell markers (PCNA, cyclins A2 and E1) at 48 hrs post CCl4 injection relative to control mice

Genotype
MGI:5284899

cn217

• Allelic Composition: Agap2^tm1Kye/Agap2^tm1Kye; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA/2

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:174775 )

N • mice exhibit normal response to high-fat diet

hyperglycemia ( J:174775 )

• in fasted mice

• in a glucose tolerance test

• in an insulin tolerance test

• in a pyruvate tolerance test

increased circulating insulin level ( J:174775 )

• in a glucose tolerance test

decreased circulating triglyceride level ( J:174775 )

• in fed mice

abnormal gluconeogenesis ( J:174775 )

• after pyruvate administration, hepatocyte glucose production is increased compared to in wild-type mice

impaired glucose tolerance ( J:174775 )

insulin resistance ( J:174775 )

• after pyruvate administration, hepatocyte glucose production is increased compared to in wild-type mice

decreased liver cholesterol level ( J:174775 )

• in fasted mice

decreased liver free fatty acids level ( J:174775 )

• in fed and fasted mice

decreased liver triglyceride level ( J:174775 )

• in fed mice

liver/biliary system

decreased liver cholesterol level ( J:174775 )

• in fasted mice

decreased liver free fatty acids level ( J:174775 )

• in fed and fasted mice

decreased liver triglyceride level ( J:174775 )

• in fed mice

growth/size/body

growth/size/body region phenotype ( J:174775 )

N • mice exhibit normal response to high-fat diet

Genotype
MGI:6718327

cn218

• Allelic Composition: Uqcc3^em1Hya/Uqcc3^em1Hya; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA/2

neoplasm

decreased incidence of induced tumors ( J:306534 )

• hypdrodynamic transfection via tail-vein injection of oncogenes myr-AKT and NRasV12 results in barely presented tumor nodules on the liver surface and normal hepatocytes and stromal cells compared to excessive nodular lesions in controls

• mice show increased survival following hypdrodynamic transfection via tail-vein injection of oncogenes myr-AKT and NRasV12 compared to controls

• liver tumor tissues show a reduction in ATP following hypdrodynamic transfection via tail-vein injection of oncogenes myr-AKT and NRasV12

homeostasis/metabolism

abnormal physiological response to hypoxia ( J:306534 )

• primary hepatoma cells from myr-AKT and NRasV12 hypdrodynamic transfected mice show slower growth in hypoxia compared with normoxia ex vivo and slower growth in hypoxia compared to controls

cellular

abnormal mitochondrial morphology ( J:306534 )

• mice show distorted and atypical mitochondria with vacuoles or abnormal cristae in the hepatocellular carcinoma cells following hypdrodynamic transfection via tail-vein injection of oncogenes myr-AKT and NRasV12; mitochondrial abnormalities are not seen in controls

liver/biliary system

liver/biliary system phenotype ( J:306534 )

N • mice show no differences in liver function from controls

Genotype
MGI:3839857

cn219

• Allelic Composition: Gt(ROSA)26Sor^{tm2(sb11)Njen}/Gt(ROSA)26Sor⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; TgTn(sb-T2/Onc)68Dla/0
• Genetic Background: involves: C57BL/6 * DBA/2 * FVB/N

neoplasm

increased hepatocellular carcinoma incidence ( J:147264 )

• seen in older males

increased liver adenoma incidence ( J:147264 )

• tumor formation is more prevalent and starts earlier in males compared to females

liver/biliary system

abnormal liver morphology ( J:147264 )

• preneoplastic nodules are first detected at about 160 days of age in males

increased hepatocellular carcinoma incidence ( J:147264 )

• seen in older males

increased liver adenoma incidence ( J:147264 )

• tumor formation is more prevalent and starts earlier in males compared to females

Genotype
MGI:5538740

cn220

• Allelic Composition: Dbi^tm2.1Smdp/Dbi^tm2.2Smdp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA * FVB/N

normal phenotype

no abnormal phenotype detected ( J:204137 )

• normal development and gross morphology at postnatal day 21

• no defect in liver adaptation to weaning is detected unlike in homozygous germ line null mice

Genotype
MGI:6388690

cn221

• Allelic Composition: Orc1^tm1.1Gle/Orc1^tm1.1Gle; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA * SJL

liver/biliary system

liver/biliary system phenotype ( J:272584 )

N • mice exhibit normal liver regeneration at 36 h and 4 d after partial hepatectomy, with a comparable restoration of liver size, reduction in hepatocyte cell density, and increase in hepatocyte proliferation and DNA content within the regenerating lobe relative to controls

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks and 3 months of age, hepatocytes are strikingly larger with larger nuclei than controls

increased hepatocyte proliferation ( J:272584 )

• in keeping with precocious endoreduplication, the number of Ki-67-, BrdU-, and P-H3-positive (Ser10 and Ser28) hepatocytes is dramatically increased at 6 weeks of age

decreased hepatocyte number ( J:272584 )

• fewer hepatocytes are observed relative to controls

• however, liver gross morphology and liver to body weight ratios are normal from 1 week to 12 months of age

cellular

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks and 3 months of age, hepatocytes are strikingly larger with larger nuclei than controls

polyploidy ( J:272584 )

• at 3 months of age, an increased proportion of hepatocytes with 8C and 16C DNA content is observed

• livers begin to endoreduplicate hepatocyte genomes prematurely (by 1 week of age) and reach maximum ploidy by 6 months of age, well in advance of controls

increased hepatocyte proliferation ( J:272584 )

• in keeping with precocious endoreduplication, the number of Ki-67-, BrdU-, and P-H3-positive (Ser10 and Ser28) hepatocytes is dramatically increased at 6 weeks of age

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely, accumulating equal to or greater than 8C DNA content prior to weaning

homeostasis/metabolism

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely, accumulating equal to or greater than 8C DNA content prior to weaning

Genotype
MGI:7408239

cn222

• Allelic Composition: Orc1^tm1.1Gle/Orc1^tm1.2Gle; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA * SJL

liver/biliary system

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks of age, hepatocytes are strikingly larger with larger nuclei than controls

decreased hepatocyte number ( J:272584 )

• fewer hepatocytes are observed relative to controls

• however, liver gross morphology is normal from 3 weeks to 3 months and liver to body weight ratios remain normal up to 6 months of age

cellular

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks of age, hepatocytes are strikingly larger with larger nuclei than controls

polyploidy ( J:272584 )

• at 3 weeks of age, an increased proportion of hepatocytes with 4C DNA content is observed

• by 3 months of age, a larger proportion of hepatocytes with 8C or greater DNA content is observed

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely

homeostasis/metabolism

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely

Genotype
MGI:5896384

cn223

• Allelic Composition: Sec24c^{tm1c(EUCOMM)Wtsi}/Sec24c^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA * SJL

growth/size/body

growth/size/body region phenotype ( J:232065 )

N • no abnormalities in growth or weight gain are detected on either a normal chow or high fat diet compared to diet-matched controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:232065 )

N • no differences in plasma cholesterol or triglyceride levels

Genotype
MGI:5566824

cn224

• Allelic Composition: Gcgr^tm2.1Mjch/Gcgr^tm2.1Mjch; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA * SJL

cellular

increased pancreatic alpha cell proliferation ( J:208604 )

• increased alpha-cell proliferation

homeostasis/metabolism

abnormal glucose homeostasis ( J:208604 )

• abrogated hyperglycemic response to acute glucagon challenge

decreased circulating glucose level ( J:208604 )

• in fasted and random samples

hypoglycemia ( J:208604 )

• mild

increased circulating glucagon level ( J:208604 )

decreased circulating insulin level ( J:208604 )

• in fasted mice

improved glucose tolerance ( J:208604 )

increased insulin sensitivity ( J:208604 )

increased bile salt level ( J:208604 )

• of total levels in plasma

endocrine/exocrine glands

increased pancreatic alpha cell proliferation ( J:208604 )

• increased alpha-cell proliferation

increased pancreatic alpha cell number ( J:208604 )

• alpha-cell hyperplasia

increased pancreatic beta cell mass ( J:208604 )

• increased beta-cell mass is secondary to enlargement of the pancreas

increased pancreas weight ( J:208604 )

growth/size/body

increased pancreas weight ( J:208604 )

Genotype
MGI:5822918

cn225

• Allelic Composition: Blvra^{tm1c(EUCOMM)Hmgu}/Blvra^{tm1c(EUCOMM)Hmgu}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6J * C57BL/6N
• Cell Lines: HEPD0510_3_B01

liver/biliary system

decreased liver glycogen level ( J:237631 )

♂ • mice fed a high-fat diet show decreased liver glycogen stores, as shown by periodic acid Schiff staining

increased liver triglyceride level ( J:237631 )

♂ • mice fed a high-fat diet show increased hepatic triglyceride levels

hepatic steatosis ( J:237631 )

♂ • mice fed a high-fat diet show significant hepatic lipid accumulation, as determined by Oil Red O staining and hepatic fat measured as % of total liver weight by Echo-MRI

homeostasis/metabolism

decreased fatty acid beta-oxidation ( J:237631 )

♂ • mice fed a high-fat diet show significantly reduced phosphorylation of ACC and AMPK as well as reduced PPARalpha expression and activity in the liver, indicating reduced burning of fat through beta-oxidation

increased fasting circulating glucose level ( J:237631 )

♂ • on a high fat diet, mice exhibit enhanced fasting hyperglycemia relative to control mice

increased circulating insulin level ( J:237631 )

♂ • on a high fat diet, mice exhibit enhanced fasting hyperinsulinemia relative to control mice

impaired glucose tolerance ( J:237631 )

♂ • mice fed a high-fat diet show higher blood glucose levels than control mice at 30, 60, and 90 min after i.p. glucose injection during glucose tolerance testing (IPGTT)

♂ • no differences are noted during insulin tolerance testing, suggesting decreased hepatic insulin sensitivity

decreased liver glycogen level ( J:237631 )

♂ • mice fed a high-fat diet show decreased liver glycogen stores, as shown by periodic acid Schiff staining

insulin resistance ( J:237631 )

♂ • on a high fat diet, mice exhibit reduced insulin signaling and hepatic insulin resistance

increased fatty acids level ( J:237631 )

♂ • hepatic steatosis is associated with enhanced hepatic expression of proteins and signaling pathways involved in fatty acid synthesis (e.g. reduced levels of phosphorylated AMPK, increased fatty acid synthase expression, and reduced levels of phosphorylated acetyl-CoA carboxylase (ACC) indicating enhanced ACC activity)

increased liver triglyceride level ( J:237631 )

♂ • mice fed a high-fat diet show increased hepatic triglyceride levels

cellular

decreased fatty acid beta-oxidation ( J:237631 )

♂ • mice fed a high-fat diet show significantly reduced phosphorylation of ACC and AMPK as well as reduced PPARalpha expression and activity in the liver, indicating reduced burning of fat through beta-oxidation

Genotype
MGI:6196884

cn226

• Allelic Composition: Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(CAG-cat,-Creg1)#Yal/0
• Genetic Background: involves: C57BL/6J * DBA

homeostasis/metabolism

abnormal circulating enzyme level ( J:263073 )

decreased circulating alanine transaminase level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased circulating alkaline phosphatase level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased circulating aspartate transaminase level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

abnormal glucose homeostasis ( J:263073 )

decreased circulating glucose level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased circulating insulin level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

impaired glucose tolerance ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

increased liver glycogen level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

insulin resistance ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

abnormal lipid homeostasis ( J:263073 )

decreased liver cholesterol level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased liver free fatty acids level ( J:263073 )

• nonesterified when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased liver triglyceride level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

liver/biliary system

increased liver glycogen level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased liver cholesterol level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased liver free fatty acids level ( J:263073 )

• nonesterified when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased liver triglyceride level ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

decreased liver weight ( J:263073 )

• when fed a high fat diet compared with non-transgenic mice fed a high fat diet

Genotype
MGI:6515651

cn227

• Allelic Composition: Usp20^em1Gpt/Usp20^em1Gpt; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6JGpt * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:299971 )

N • mice fed a high-fat and high-sucrose diet exhibit normal respiratory exchange ratio

decreased circulating glucose level ( J:299971 )

• in fasted and refed mice

decreased fasting circulating glucose level ( J:299971 )

• in fasted and refed mice

decreased circulating insulin level ( J:299971 )

• in refed mice

• however, fasted mice exhibit normal levels

decreased circulating cholesterol level ( J:299971 )

• in fasted and refed mice

• treatment with GSK2643943A does not alter cholesterol levels

• however, adenoviral expression of HMGCR with the point mutation K248R exhibit rescued phenotype

decreased circulating HDL cholesterol level ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

decreased circulating LDL cholesterol level ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

decreased circulating free fatty acids level ( J:299971 )

• in fasted and refed mice

decreased circulating triglyceride level ( J:299971 )

• in fasted and refed mice

• treatment with GSK2643943A does not alter triglyceride levels

• however, adenoviral expression of HMGCR with the point mutation K248R exhibit rescued phenotype

decreased circulating VLDL triglyceride level ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

increased body surface temperature ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

increased energy expenditure ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

• treatment with GSK2643943A does not ameliorate energy expenditure

• however, adenoviral expression of HMGCR with the point mutation K248R exhibit rescued phenotype

abnormal enzyme/coenzyme level ( J:299971 )

• increased liver levels of HMG-CoA and succinate

• decreased liver levels of succinyl-CoA

abnormal circulating enzyme level ( J:299971 )

• doubled serum succinate levels

increased oxygen consumption ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

improved glucose tolerance ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

• treatment with GSK2643943A does not alter glucose clearance

• however, adenoviral expression of HMGCR with the point mutation K248R exhibit rescued phenotype

increased insulin sensitivity ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

decreased liver cholesterol level ( J:299971 )

• in fasted and refed mice

decreased liver triglyceride level ( J:299971 )

• in fasted and refed mice

• decreased VLDL, LDL, and HDL

liver/biliary system

abnormal liver morphology ( J:299971 )

• reduced fat accumulation when mice are fed a high-fat and high-sucrose diet

decreased liver cholesterol level ( J:299971 )

• in fasted and refed mice

decreased liver triglyceride level ( J:299971 )

• in fasted and refed mice

• decreased VLDL, LDL, and HDL

decreased liver weight ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

growth/size/body

decreased body fat mass ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

• however, adenoviral expression of HMGCR with the point mutation K248R exhibit rescued phenotype

decreased body weight ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

• however, lean body mass to body weight is normal

behavior/neurological

behavior/neurological phenotype ( J:299971 )

N • mice fed a high-fat and high-sucrose diet exhibit normal physical activity

adipose tissue

decreased body fat mass ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

• however, adenoviral expression of HMGCR with the point mutation K248R exhibit rescued phenotype

decreased fat cell size ( J:299971 )

• reduced area

decreased white adipose tissue mass ( J:299971 )

• when mice are fed a high-fat and high-sucrose diet

Genotype
MGI:6515654

cn228

• Allelic Composition: Hmgcr^em1Bcgen/Hmgcr^em1Bcgen; Usp20^em1Gpt/Usp20^em1Gpt; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6JGpt * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:299971 )

N • mice fed a high-fat and high-sucrose diet exhibit normal total cholesterol levels in fasted and refed mice, oxygen consumption, and glucose tolerance

increased circulating triglyceride level ( J:299971 )

• in fasted and refed mice fed a high-fat and high-sucrose diet

Genotype
MGI:6384968

cn229

• Allelic Composition: A1cf^{tm1c(EUCOMM)Hmgu}/A1cf^{tm1c(EUCOMM)Hmgu}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6N * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:281365 )

N • mice exhibit normal serum levels alanine transaminase, bile, and non-esterified free fatty acids

decreased susceptibility to diet-induced obesity ( J:281365 )

• mice fed a high-fructose diet exhibit reduced body weight and blood glucose levels compared with wild-type mice

abnormal blood homeostasis ( J:281365 )

• increased blood and urine fructose level in mice fed a high-fructose diet

decreased circulating glucose level ( J:281365 )

• mice fed a high-fructose diet exhibit reduced body weight and blood glucose levels compared with wild-type mice

decreased fasting circulating glucose level ( J:281365 )

• in mice fasted for either 6 h or overnight

• however, fed mice exhibit normal levels

decreased circulating insulin level ( J:281365 )

• in mice fed ad libitum

decreased circulating ketone body level ( J:281365 )

• in fasted mice

increased circulating cholesterol level ( J:281365 )

• modestly

increased circulating triglyceride level ( J:281365 )

• moderately in fed mice

impaired gluconeogenesis ( J:281365 )

• decreased hepatic glucose production determined by an intraperitoneal sodium pyruvate tolerance test

• mice fail to exhibit glucose production in response to a fructose load unlike wild-type

• reduced glycogen-stimulated glucose production in hepatocyte

improved glucose tolerance ( J:281365 )

• in mice fed standard chow or a high-fructose diet

increased liver glycogen level ( J:281365 )

• in fed, fasted or refed mice

increased insulin sensitivity ( J:281365 )

• in mice fed a high-fructose diet

decreased liver triglyceride level ( J:281365 )

• in fasted mice

• in mice fed a high-fructose diet

abnormal urine homeostasis ( J:281365 )

• increased blood and urine fructose level in mice fed a high-fructose diet

decreased urine uric acid level ( J:281365 )

• in mice fed a high-fructose diet

liver/biliary system

increased liver glycogen level ( J:281365 )

• in fed, fasted or refed mice

decreased liver triglyceride level ( J:281365 )

• in fasted mice

• in mice fed a high-fructose diet

decreased liver weight ( J:281365 )

• in mice fed standard chow or a high-fructose diet

abnormal hepatobiliary system physiology ( J:281365 )

• mice fed a high-fructose diet exhibit increased intrahepatic ATP levels and decreased intrahepatic ADP levels compared with wild-type mice

renal/urinary system

abnormal urine homeostasis ( J:281365 )

• increased blood and urine fructose level in mice fed a high-fructose diet

decreased urine uric acid level ( J:281365 )

• in mice fed a high-fructose diet

growth/size/body

decreased susceptibility to diet-induced obesity ( J:281365 )

• mice fed a high-fructose diet exhibit reduced body weight and blood glucose levels compared with wild-type mice

Genotype
MGI:5751747

cn230

• Allelic Composition: Clk2^tm1.1Ppgr/Clk2^tm1.1Ppgr; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6NTac * FVB/N

homeostasis/metabolism

abnormal fatty acid oxidation ( J:229283 )

• mice fed a high fat diet exhibit increased fatty acid and ketogenesis with increased beta-hydroxybutyrate serum levels in fasted mice

decreased respiratory quotient ( J:229283 )

• in fasted high-fat diet fed mice

decreased liver triglyceride level ( J:229283 )

• in fasted high-fat diet fed mice, but not refed mice

liver/biliary system

decreased liver triglyceride level ( J:229283 )

• in fasted high-fat diet fed mice, but not refed mice

cellular

abnormal fatty acid oxidation ( J:229283 )

• mice fed a high fat diet exhibit increased fatty acid and ketogenesis with increased beta-hydroxybutyrate serum levels in fasted mice

Genotype
MGI:4353035

cn231

• Allelic Composition: Antxr2^tm1.1Lepp/Antxr2^tm1.1Lepp; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

mortality/aging ( J:150952 )

N • in contrast to null mice, mice with conditional deletion in the liver are as susceptible as wild-type controls to anthrax lethal toxin induced lethality

Genotype
MGI:7611657

cn232

• Allelic Composition: Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tor1aip1^tm1.1Wtd/Tor1aip1^tm1.1Wtd
• Genetic Background: Not Specified

liver/biliary system

abnormal hepatocyte morphology ( J:345574 )

• most (64 +/- 5%) nuclei contain 2 or more lipid droplets