Phenotypes associated with this allele

• Allele Symbol: Tg(Ckmm-cre)5Khn
• Allele Name: transgene insertion 5, C Ronald Kahn
• Allele ID: MGI:2182095
• Summary: 110 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Adipor1^tm2Tka/Adipor1^tm2Tka Tg(Ckmm-cre)5Khn/0	B6.Cg-Adipor1^tm2Tka Tg(Ckmm-cre)5Khn	MGI:4457491
cn2	Fxn^em2Lutzy/Fxn^em2.1Lutzy Tg(Ckmm-cre)5Khn/?	B6.Cg-Fxn^em2Lutzy Fxn^em2.1Lutzy Tg(Ckmm-cre)5Khn/J	MGI:5827807
cn3	Nuak1^tm1Esu/Nuak1^tm1Esu Tg(Ckmm-cre)5Khn/0	B6.Cg-Nuak1^tm1Esu Tg(Ckmm-cre)5Khn	MGI:5428916
cn4	Sdhaf4^em1Bcgen/Sdhaf4^em1Bcgen Tg(Ckmm-cre)5Khn/0	B6.Cg-Sdhaf4^em1Bcgen Tg(Ckmm-cre)5Khn	MGI:7596076
cn5	Sgca^tm2Kcam/Sgca^tm2Kcam Tg(Ckmm-cre)5Khn/0	either: (involves: 129S4/SvJae * 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6J * FVB)	MGI:3772354
cn6	Plec^tm1Gwi/Plec^tm4Gwi Tg(Ckmm-cre)5Khn/?	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB	MGI:3800799
cn7	Atg5^tm1Myok/Atg5^tm1Myok Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6 * FVB	MGI:6151158
cn8	Bcar1^tm2.1Homy/Bcar1^tm2.1Homy Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * C57BL/6	MGI:5495141
cn9	Srf^tm2.1Nor/Srf^tm2.1Nor Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3530888
cn10	Cebpb^tm1Nerl/Cebpb^tm1Nerl Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:4366867
cn11	Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:6151150
cn12	Prkci^tm1Rfar/Prkci^tm1Rfar Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:3721144
cn13	Prkci^tm1Rfar/Prkci^+ Tg(Ckmm-cre)5Khn/?	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:3721145
cn14	Abhd5^tm1Rze/Abhd5^tm1Rze Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:5502413
cn15	Slc7a5^tm1.1Daca/Slc7a5^tm1.1Daca Tg(Ckmm-cre)5Khn/?	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5618526
cn16	Plec^tm4Gwi/Plec^tm4Gwi Tg(Ckmm-cre)5Khn/?	involves: 129P2/OlaHsd * C57BL/6J * FVB	MGI:3800798
cn17	Atg7^tm1Tchi/Atg7^tm1Tchi Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj * FVB	MGI:6151152
cn18	Pdha1^tm1Ptl/Pdha1^+ Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:3843872
cn19	Pdha1^tm1Ptl/Y Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:3843870
cn20	Glul^tm3Whla/Glul^tm1Whla Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:4462798
cn21	Pten^tm2Mak/Pten^tm2Mak Tg(Ckmm-cre)5Khn/0 Tg(Myh6-Pik3ca)1Siz/0	involves: 129P2/OlaHsd * FVB	MGI:3619942
cn22	Pik3cg^tm1Pngr/Pik3cg^tm1Pngr Pten^tm2Mak/Pten^tm2Mak Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:3619937
cn23	Aifm1^tm2Pngr/Y Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:3687267
cn24	Pten^tm2Mak/Pten^tm2Mak Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:3619927
cn25	Glul^tm3Whla/Glul^tm3Whla Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:4462799
cn26	Parl^tm1Bdes/Parl^tm1Bdes Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:6280693
cn27	Lama2^tm1Eeng/Lama2^tm1Eeng Smdt1^tm1c(EUCOMM)Wtsi/Smdt1^tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/6N * FVB	MGI:6458049
cn28	Erbb2^tm3(Erbb2)Mul/Erbb2^tm3(Erbb2)Mul Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * BALB/c * FVB	MGI:2449942
cn29	Mterf4^tm1.1Lrsn/Mterf4^tm1.1Lrsn Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB	MGI:5292478
cn30	Mterf3^tm1.1Lrsn/Mterf3^tm1.1Lrsn Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB * SJL	MGI:3839275
cn31	Tfb1m^tm1.1Lrsn/Tfb1m^tm1.1Lrsn Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB * SJL	MGI:3844252
cn32	Hif1a^tm3Rsjo/Hif1a^tm3Rsjo Tg(Ckmm-cre)5Khn/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:3621470
cn33	Mstn^tm1Mgs/Mstn^tm1Mgs Tg(Ckmm-cre)5Khn/?	involves: 129S1/Sv * 129X1/SvJ * CD-1 * FVB	MGI:2661075
cn34	Dag1^tm2Kcam/Dag1^tm2Kcam Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:2450243
cn35	Rr27^tm1Kpfe/Rr27^tm1Kpfe Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:3722124
cn36	Ptpn11^tm1Gsf/Ptpn11^tm1Gsf Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:5906203
cn37	Lrpprc^tm1.1Lrsn/Lrpprc^tm1.1Lrsn Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:5438914
cn38	Esr1^tm4.2Ksk/Esr1^tm4.2Ksk Mir22^tm1Boet/Mir22^tm1Boet Tg(Ckmm-cre)5Khn/0	involves: 129S2/SvPas * C57BL/6 * FVB	MGI:6275157
cn39	Scyl1^tm1Spel/Scyl1^tm1Spel Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5469974
cn40	Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6 * FVB	MGI:3775309
cn41	Mapk8^tm1Jcbr/Mapk8^tm1Jcbr Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6 * FVB	MGI:5494712
cn42	Dgcr8^tm1.1Blel/Dgcr8^tm1.1Blel Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6 * FVB	MGI:4821347
cn43	Insr^tm1Khn/Insr^tm1Dac Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6J * FVB	MGI:2389586
cn44	Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6J * FVB	MGI:2389585
cn45	Akt1^tm2Mbb/Akt1^tm2Mbb Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6J * FVB	MGI:5317893
cn46	Smdt1^tm1c(EUCOMM)Wtsi/Smdt1^tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6N * FVB	MGI:6458047
cn47	Slc2a4^tm1Abel/Slc2a4^tm1Abel Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * FVB	MGI:3663416
cn48	Slc2a4^tm1Abel/Slc2a4^+ Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * FVB	MGI:3663418
cn49	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ckmm-cre)5Khn/?	involves: 129S4/SvJae * FVB	MGI:4944271
cn50	Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJaeSor * FVB	MGI:5829560
cn51	Gt(ROSA)26Sor^tm1(CAG-GCaMP5)Ryba/Gt(ROSA)26Sor^+ Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJaeSor * FVB	MGI:5829563
cn52	Pik3r1^tm1Lca/Pik3r1^tm1Lca Pik3r2^tm1Lca/Pik3r2^tm1Lca Tg(Ckmm-cre)5Khn/0	involves: 129S6/SvEvTac * C57BL/6 * FVB	MGI:3609012
cn53	Hjv^tm1Kpan/Hjv^tm1Kpan Tg(Ckmm-cre)5Khn/0	involves: 129S6/SvEvTac * C57BL/6 * FVB	MGI:5792903
cn54	Pik3r1^tm1Lca/Pik3r1^tm1Lca Tg(Ckmm-cre)5Khn/0	involves: 129S6/SvEvTac * C57BL/6 * FVB	MGI:3609011
cn55	Neb^tm2Hgra/Neb^tm2Hgra Tg(Ckmm-cre)5Khn/0	involves: 129S6/SvEvTac * FVB	MGI:5883288
cn56	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1.1Zhe/App^tm1.1Zhe Tg(Ckmm-cre)5Khn/0	involves: 129S7/SvEvBrd * C57BL/6J * FVB	MGI:4359072
cn57	Fkbp1a^tm1Slh/Fkbp1a^tm1Slh Tg(Ckmm-cre)5Khn/0	involves: 129S7/SvEvBrd * FVB	MGI:5293356
cn58	Fkbp1a^tm1.1Shou/Fkbp1a^tm1Zuk Tg(Ckmm-cre)5Khn/0	involves: 129S7/SvEvBrd * FVB	MGI:5490256
cn59	Fkbp1a^tm1Zuk/Fkbp1a^tm1Slh Tg(Ckmm-cre)5Khn/0	involves: 129S7/SvEvBrd * FVB	MGI:3521579
cn60	Pnpla2^tm1Eek/Pnpla2^tm1Eek Tg(Ckmm-cre)5Khn/0	involves: 129S * FVB/N	MGI:5294403
cn61	Fktn^tm1Kcam/Fktn^tm1Kcam Tg(Ckmm-cre)5Khn/?	involves: 129S/SvEv * FVB	MGI:5435675
cn62	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr^+ Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB	MGI:3775313
cn63	Igf1r^tm1.1Mhz/Igf1r^+ Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB	MGI:3775310
cn64	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB	MGI:3775311
cn65	Slc2a4^tm1Abel/Slc2a4^tm1Abel Tg(Ckmm-cre)5Khn/?	involves: 129/Sv * C57BL/6	MGI:3029365
cn66	Ptpn11^tm1Yan/Ptpn11^tm1Yan Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * C57BL/6 * FVB	MGI:3697622
cn67	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * C57BL/6 * FVB	MGI:3775312
cn68	Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw Tg(Ckmm-cre)5Khn/?	involves: BALB/c	MGI:2677593
cn69	Bud23^em2Asil/Bud23^em2Asil Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:6693480
cn70	Oma1^tm1Tlan/Oma1^tm1Tlan Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * C57BL/6NCrl * FVB	MGI:5805262
cn71	Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * C57BL/6NCrl * FVB	MGI:5805260
cn72	Cfl2^tm1Itl/Cfl2^tm1Itl Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * C57BL/6NTac * FVB/N	MGI:5316089
cn73	Sod2^tm1Shs/Sod2^tm1Shs Tg(Ckmm-cre)5Khn/0	involves: C57BL/6CrSlc * FVB	MGI:5907992
cn74	Gt(ROSA)26Sor^tm1(CAG-MAP2K7*/MAPK8,-EGFP)Ftw/Gt(ROSA)26Sor^+ Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:5494711
cn75	Txnip^tm1Road/Txnip^tm1Road Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:3809846
cn76	Lig3^tm1.1Pmc/Lig3^tm1.1Pmc Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:4946937
cn77	Prkab1^tm1Grst/Prkab1^tm1Grst Prkab2^tm1Grst/Prkab2^tm1Grst Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:5293380
cn78	Prkab2^tm1Grst/Prkab2^tm1Grst Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:5293381
cn79	Twnk^tm1.1Lrsn/Twnk^tm1.1Lrsn Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:5496891
cn80	Fktn^tm3.1Ttd/Fktn^tm3.1Ttd Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:5514355
cn81	Atf4^tm1.1Cmad/Atf4^tm1.1Cmad Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:5550389
cn82	Fnip1^tm1.1Baba/Fnip1^tm1.1Baba Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:5897113
cn83	Cnot1^tm1Tya/Cnot1^tm1Tya Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB	MGI:6151160
cn84	Nsun4^tm1.2Arte/Nsun4^tm1.2Arte Tg(Ckmm-cre)5Khn/0	involves: C57BL/6 * FVB/N * SJL	MGI:6294482
cn85	Gpcpd1^tm1c(EUCOMM)Hmgu/Gpcpd1^tm1c(EUCOMM)Hmgu Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * C57BL/6N * FVB	MGI:7610682
cn86	Hmox1^tm1.1Hes/Hmox1^tm1.1Hes Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * C57BL/6N * FVB/N	MGI:5660650
cn87	Gfpt1^tm1c(EUCOMM)Wtsi/Gfpt1^tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * C57BL/6N * SJL/J	MGI:6277926
cn88	Crat^tm1.1Pbrc/Crat^tm1.1Pbrc Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * FVB	MGI:5427431
cn89	Myhas^tm1Bcgen/Myhas^tm1Bcgen Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * FVB	MGI:7545578
cn90	Bmal1^tm1.1Shbi/Bmal1^tm1.1Shbi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * FVB	MGI:5613395
cn91	Musk^tm1Vwi/Musk^tm1Vwi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * FVB	MGI:3622117
cn92	Musk^tm1Vwi/Musk^tm1.1Vwi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6J * FVB	MGI:3622118
cn93	Gt(ROSA)26Sor^tm1(CAG-LMNA*)Cyh/Gt(ROSA)26Sor^+ Tg(Ckmm-cre)5Khn/0	involves: C57BL/6JNarl * FVB	MGI:6407437
cn94	Mtif3^tm1c(EUCOMM)Wtsi/Mtif3^tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N	MGI:7580966
cn95	Pik3c3^tm1c(EUCOMM)Wtsi/Pik3c3^tm1c(EUCOMM)Wtsi Tg(CAG-EGFP/Map1lc3b)53Nmz/0 Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N * C57BL/6NCrj * FVB/N	MGI:5427445
cn96	Fis1^tm1.1Itl/Fis1^tm1.1Itl Tg(CAG-EGFP/Map1lc3b)53Nmz/0 Tg(Ckmm-cre)5Khn/0	involves: C57BL/6NCrlj * C57BL/6NTac * DBA/2 * FVB	MGI:6444642
cn97	Atg7^tm1Tchi/Atg7^tm1Tchi Cnot1^tm1Tya/Cnot1^tm1Tya Tg(Ckmm-cre)5Khn/0	involves: C57BL/6NCrlj * CBA/JNCrlj * FVB	MGI:6151162
cn98	Elac2^tm1c(EUCOMM)Wtsi/Elac2^tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N * FVB	MGI:7433065
cn99	Prorp^tm1.1Afi/Prorp^tm1.1Afi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N * FVB	MGI:6282903
cn100	Rexo2^tm1.1Arte/Rexo2^tm1.1Arte Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N * FVB	MGI:6856855
cn101	Tefm^tm1.1Lrsn/Tefm^tm1.1Lrsn Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N * FVB	MGI:6360162
cn102	Polrmt^tm1.1Arte/Polrmt^tm1.1Arte Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N * FVB	MGI:6147657
cn103	Pik3c3^tm1c(EUCOMM)Wtsi/Pik3c3^tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0	involves: C57BL/6N * FVB/N	MGI:5427444
cn104	Mgme1^tm1.1Lrsn/Mgme1^tm1.1Lrsn Tg(Ckmm-cre)5Khn/0	involves: C57BL/6NTac * FVB	MGI:6151396
cn105	Fis1^tm1.1Itl/Fis1^tm1.1Itl Tg(Ckmm-cre)5Khn/0	involves: C57BL/6NTac * FVB	MGI:6444640
cn106	Appl2^tm1Smoc/Appl2^tm1Smoc Tg(Ckmm-cre)5Khn/0	involves: FVB	MGI:5762817
cn107	Sod2^tm1Shs/Sod2^tm1Shs Tg(Ckmm-cre)5Khn/0	involves: FVB	MGI:5907999
cn108	Stk11^tm1Keis/Stk11^tm1Keis Tg(Ckmm-cre)5Khn/0	involves: FVB	MGI:3580297
cn109	Plrg1^tm2Jcbr/Plrg1^tm2Jcbr Tg(Ckmm-cre)5Khn/0	involves: FVB	MGI:3848249
cn110	Ttn^tm1Her/Ttn^tm1Her Tg(Ckmm-cre)5Khn/0	Not Specified	MGI:2651647

Genotype
MGI:4457491

cn1

• Allelic Composition: Adipor1^tm2Tka/Adipor1^tm2Tka; Tg(Ckmm-cre)5Khn/0
• Genetic Background: B6.Cg-Adipor1^tm2Tka Tg(Ckmm-cre)5Khn

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

homeostasis/metabolism

impaired exercise endurance ( J:159462 )

• mice exhibit lower muscle endurance in an involuntary physical exercise test compared with wild-type mice

decreased oxygen consumption ( J:159462 )

• in skeletal muscle

abnormal glucose homeostasis ( J:159462 )

increased circulating glucose level ( J:159462 )

• following glucose administration

increased circulating insulin level ( J:159462 )

• following glucose administration

insulin resistance ( J:159462 )

• muscles exhibit decreased insulin sensitivity compared with wild-type mice with decreased glucose disposal and glucose infusion rate

• however, treatment with resveratrol or two weeks of exercise ameliorates insulin resistance while treatment with MnTBAP produces a trend towards amelioration of insulin resistance

increased skeletal muscle triglyceride level ( J:159462 )

cellular

abnormal skeletal muscle fiber mitochondrial morphology ( J:159462 )

• skeletal muscle exhibits a decrease in mitochondrial DNA content compared with wild-type muscle

• however, treatment with resveratrol, Bay-K 8644 (a calcium-channel opener), or two weeks of exercise increased mitochondrial content

oxidative stress ( J:159462 )

• skeletal muscle cells exhibit a decrease in beta oxidation and an increased in hydrogen peroxide level compared with wild-type cells

• however, treatment with MnTBAP reduces hydrogen peroxide levels

muscle

abnormal skeletal muscle fiber mitochondrial morphology ( J:159462 )

• skeletal muscle exhibits a decrease in mitochondrial DNA content compared with wild-type muscle

• however, treatment with resveratrol, Bay-K 8644 (a calcium-channel opener), or two weeks of exercise increased mitochondrial content

increased skeletal muscle triglyceride level ( J:159462 )

abnormal skeletal muscle fiber type ratio ( J:159462 )

• soleus muscle exhibit a decrease in type I fibers compared with wild-type muscles

behavior/neurological

impaired exercise endurance ( J:159462 )

• mice exhibit lower muscle endurance in an involuntary physical exercise test compared with wild-type mice

Genotype
MGI:5827807

cn2

• Allelic Composition: Fxn^em2Lutzy/Fxn^em2.1Lutzy; Tg(Ckmm-cre)5Khn/?
• Genetic Background: B6.Cg-Fxn^em2Lutzy Fxn^em2.1Lutzy Tg(Ckmm-cre)5Khn/J

cardiovascular system

increased heart left ventricle weight ( J:101977 )

• left ventricular mass is increased as compared to controls by 9 weeks of age

decreased cardiac muscle contractility ( J:101977 )

• decreased ejection fraction as compared to controls by 7 weeks of age

• decreased fractional shortening as compared to controls by 7 weeks of age

decreased heart rate ( J:101977 )

• decreased heart rate by 7 weeks of age

cardiomyopathy ( J:101977 )

• progressive cardiomyopathy

mortality/aging

premature death ( J:101977 )

• mean survival is 86 +/- days of age

muscle

decreased cardiac muscle contractility ( J:101977 )

• decreased ejection fraction as compared to controls by 7 weeks of age

• decreased fractional shortening as compared to controls by 7 weeks of age

cardiomyopathy ( J:101977 )

• progressive cardiomyopathy

Genotype
MGI:5428916

cn3

• Allelic Composition: Nuak1^tm1Esu/Nuak1^tm1Esu; Tg(Ckmm-cre)5Khn/0
• Genetic Background: B6.Cg-Nuak1^tm1Esu Tg(Ckmm-cre)5Khn

muscle

muscle phenotype ( J:185463 )

N • no differences are detected in heart or soleus muscle weights and soleus myocyte cross sections are similar to controls on both normal chow and high fat diets

abnormal muscle cell glucose uptake ( J:185463 )

• in soleus muscle cells from mice on a high fat diet glucose uptake is similar to mice on a normal chow diet unlike in wild-type mice where the high fat diet impairs glucose uptake

increased skeletal muscle glycogen level ( J:185463 )

• in mice fed a normal chow or high fat diet compared to diet matched controls

homeostasis/metabolism

decreased circulating glucose level ( J:185463 )

• in mice on a high fat diet, fasting glucose levels are reduced at 13 - 15 and 18-19 weeks of age compared to diet matched controls

• no difference in glucose levels compared to controls is detected in mice on a normal chow diet

improved glucose tolerance ( J:185463 )

• in mice on a high fat diet compared to diet matched controls

increased skeletal muscle glycogen level ( J:185463 )

• in mice fed a normal chow or high fat diet compared to diet matched controls

increased insulin sensitivity ( J:185463 )

• in mice on a high fat diet compared to diet matched controls

cellular

abnormal muscle cell glucose uptake ( J:185463 )

• in soleus muscle cells from mice on a high fat diet glucose uptake is similar to mice on a normal chow diet unlike in wild-type mice where the high fat diet impairs glucose uptake

Genotype
MGI:7596076

cn4

• Allelic Composition: Sdhaf4^em1Bcgen/Sdhaf4^em1Bcgen; Tg(Ckmm-cre)5Khn/0
• Genetic Background: B6.Cg-Sdhaf4^em1Bcgen Tg(Ckmm-cre)5Khn

mortality/aging

premature death ( J:345348 )

• none survive past 12 weeks of age

• treatment with sodium fumarate dibasic or Mdivi-1 (a specific Dnm1l inhibitor) to target mitochondria substantially prolongs the survival of the mice

cardiovascular system

abnormal myocardial fiber morphology ( J:345348 )

• severe abnormalities in myofibril/sarcomere organization and intramitochondrial structure at 8 weeks of age

abnormal myocardial fiber mitochondrial morphology ( J:345348 )

• at 8 weeks of age cristae malformations, electron-dense inclusions and hypodense compartments are seen

• at 8 weeks of age the number of mitochondria is increased and the size is decreased

• despite the increase in number of mitochondria the amount of mtDNA is reduced

• treatment with sodium fumarate dibasic or Mdivi-1 (a specific Dnm1l inhibitor) improves mitochondrial morphology

decreased myocardial fiber mitochondrial DNA content ( J:345348 )

• in cardiomyocytes at 8 weeks of age

thick myocardium ( J:345348 )

• thickening of the cardiac muscle by 3-4 weeks of age

enlarged heart ( J:345348 )

increased heart weight ( J:345348 )

• starting at 3 weeks of age

dilated heart ventricle ( J:345348 )

• develops at later stages

cardiac fibrosis ( J:345348 )

• present at 7 weeks but not at 4 weeks of age

dilated cardiomyopathy ( J:345348 )

• at later stages

• upregulation of pathological markers is seen primarily in the left ventricle

abnormal cardiac muscle contractility ( J:345348 )

• deregulated cardiac contraction

• treatment with Mdivi-1 (a specific Dnm1l inhibitor) improves cardiac function

decreased ventricle muscle contractility ( J:345348 )

• decrease in left ventricular fractional shortening

growth/size/body

enlarged heart ( J:345348 )

increased heart weight ( J:345348 )

• starting at 3 weeks of age

decreased body weight ( J:345348 )

• lower body weights in mice older than 6 weeks

• no difference in body weight is detected during the first 6 weeks of life

• ratio of tibialis anterior muscle weight to body weight is similar to controls

cellular

abnormal myocardial fiber mitochondrial morphology ( J:345348 )

• at 8 weeks of age cristae malformations, electron-dense inclusions and hypodense compartments are seen

• at 8 weeks of age the number of mitochondria is increased and the size is decreased

• despite the increase in number of mitochondria the amount of mtDNA is reduced

• treatment with sodium fumarate dibasic or Mdivi-1 (a specific Dnm1l inhibitor) improves mitochondrial morphology

decreased myocardial fiber mitochondrial DNA content ( J:345348 )

• in cardiomyocytes at 8 weeks of age

abnormal mitochondrial physiology ( J:345348 )

• mitochondrial dysfunction in the heart indicated by expression analysis, increase in protein oxidation, and decreases in TCA cycle related metabolites

• analysis of posttranslational modification of Dnm1l and other results suggest an increase in mitochondrial fission

abnormal tricarboxylic acid cycle ( J:345348 )

• deregulated TCA cycle in cardiomyocytes

muscle

abnormal myocardial fiber morphology ( J:345348 )

• severe abnormalities in myofibril/sarcomere organization and intramitochondrial structure at 8 weeks of age

abnormal myocardial fiber mitochondrial morphology ( J:345348 )

• at 8 weeks of age cristae malformations, electron-dense inclusions and hypodense compartments are seen

• at 8 weeks of age the number of mitochondria is increased and the size is decreased

• despite the increase in number of mitochondria the amount of mtDNA is reduced

• treatment with sodium fumarate dibasic or Mdivi-1 (a specific Dnm1l inhibitor) improves mitochondrial morphology

decreased myocardial fiber mitochondrial DNA content ( J:345348 )

• in cardiomyocytes at 8 weeks of age

thick myocardium ( J:345348 )

• thickening of the cardiac muscle by 3-4 weeks of age

dilated cardiomyopathy ( J:345348 )

• at later stages

• upregulation of pathological markers is seen primarily in the left ventricle

abnormal cardiac muscle contractility ( J:345348 )

• deregulated cardiac contraction

• treatment with Mdivi-1 (a specific Dnm1l inhibitor) improves cardiac function

decreased ventricle muscle contractility ( J:345348 )

• decrease in left ventricular fractional shortening

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:345348

Genotype
MGI:3772354

cn5

• Allelic Composition: Sgca^tm2Kcam/Sgca^tm2Kcam; Tg(Ckmm-cre)5Khn/0
• Genetic Background: either: (involves: 129S4/SvJae * 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6J * FVB)

muscle

muscle phenotype ( J:130252 )

N • conditional mutants fail to develop muscular dystrophy pathology; striated and cardiac muscle show expression of mutant alpha-sarcoglycan, as well as sarcospan

N • percentage of fibers with centrally located nuclei are normalized to levels of heterozygous non-transgenic controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:130252 )

N • serum creatine kinase levels are normalized

Genotype
MGI:3800799

cn6

• Allelic Composition: Plec^tm1Gwi/Plec^tm4Gwi; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB

mortality/aging

decreased survivor rate ( J:137067 )

• decreased survival rates starting at 6 months of age

muscle

muscle phenotype ( J:137067 )

N • no abnormal muscle phenotype in early months of life

N • extensor digitorum longus is normal at 16 months of age

abnormal myocardial fiber morphology ( J:137067 )

• focal disorganization of contractile apparatus

abnormal muscle fiber mitochondrial morphology ( J:137067 )

• mitochondria lose association with Z-discs of muscle fibers

• mitochondria found in focal aggregates in sarcoplasm and subsarcolemmal regions

• numbers of mitochondria in muscle fibers is reduced

abnormal soleus morphology ( J:137067 )

• soleus muscle appears pale at 8 weeks of age and pathological changes are seen at 6 months

abnormal sarcolemma morphology ( J:137067 )

• detached from the contractile apparatus in the soleus and the diaphragm

• 61% of fibers with focal detachments at 8 weeks

abnormal skeletal muscle fiber morphology ( J:137067 )

• inner structure of fibers is disorganized

• eosinophylic inclusions are present under the sarcolemma

skeletal muscle fiber necrosis ( J:137067 )

• numerous necrotic fibers are found in the soleus at 8 weeks

increased skeletal muscle fiber size ( J:137067 )

• hypertrophic and split fibers in both the soleus and diaphragm in older mice

centrally nucleated skeletal muscle fibers ( J:137067 )

• centrally nucleated fibers are present in the soleus at 8 weeks

• at 3 months, 35% of fibers in exercised mice are centrally nucleated (45% at 12 months)

decreased skeletal muscle fiber number ( J:137067 )

• slight reduction in total number of fibers

decreased skeletal muscle mass ( J:137067 )

• loss of muscle mass observed in some mice at 16 months of age

skeletal muscle fiber atrophy ( J:137067 )

• atrophic fibers found in then soleus at 1 year

cardiovascular system

cardiovascular system phenotype ( J:137067 )

N • no heart pathologies at 12 months

N • no dilated or hypertrophic cardiomyopathies at 16 months of age

abnormal heart morphology ( J:137067 )

• increased connective tissue at 16 months of age

abnormal myocardial fiber morphology ( J:137067 )

• focal disorganization of contractile apparatus

homeostasis/metabolism

impaired exercise endurance ( J:137067 )

• decreased endurance during voluntary wheel running

cellular

abnormal muscle fiber mitochondrial morphology ( J:137067 )

• mitochondria lose association with Z-discs of muscle fibers

• mitochondria found in focal aggregates in sarcoplasm and subsarcolemmal regions

• numbers of mitochondria in muscle fibers is reduced

skeletal muscle fiber necrosis ( J:137067 )

• numerous necrotic fibers are found in the soleus at 8 weeks

behavior/neurological

impaired exercise endurance ( J:137067 )

• decreased endurance during voluntary wheel running

limbs/digits/tail

abnormal soleus morphology ( J:137067 )

• soleus muscle appears pale at 8 weeks of age and pathological changes are seen at 6 months

Genotype
MGI:6151158

cn7

• Allelic Composition: Atg5^tm1Myok/Atg5^tm1Myok; Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6 * FVB

homeostasis/metabolism

abnormal autophagosome formation ( J:260012 )

• impaired autophagosome formation

mortality/aging

premature death ( J:260012 )

cardiovascular system

increased heart weight ( J:260012 )

decreased cardiac muscle contractility ( J:260012 )

prolonged QT interval ( J:260012 )

cellular

abnormal autophagosome formation ( J:260012 )

• impaired autophagosome formation

muscle

decreased cardiac muscle contractility ( J:260012 )

growth/size/body

increased heart weight ( J:260012 )

Genotype
MGI:5495141

cn8

• Allelic Composition: Bcar1^tm2.1Homy/Bcar1^tm2.1Homy; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

muscle

muscle phenotype ( J:195063 )

N • mice exhibit normal basic skeletal muscle properties and exercise-induced fiber-type transformation

Genotype
MGI:3530888

cn9

• Allelic Composition: Srf^tm2.1Nor/Srf^tm2.1Nor; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

Severe runting and skeletal muscle abnormalities in Srf^tm2.1Nor/Srf^tm2.1Nor Tg(Ckmm-cre)5Khn/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:96122 )

• mutants are born alive and are able to feed but die by P7

behavior/neurological

lethargy ( J:96122 )

• starts around P3

growth/size/body

postnatal growth retardation ( J:96122 )

• starts around P3

muscle

abnormal skeletal muscle fiber morphology ( J:96122 )

• at P3 myofibers are thinner than normal; however, no cardiac abnormalities are seen

• less severe than in homozygous Srf conditional mutants hemizygous for Tg(Myog-cre)1Eno

Genotype
MGI:4366867

cn10

• Allelic Composition: Cebpb^tm1Nerl/Cebpb^tm1Nerl; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:153686 )

N • mice exhibit normal muscle regeneration in response to treatment with cardiotoxin

muscle

muscle phenotype ( J:153686 )

N • mice exhibit normal muscle regeneration in response to treatment with cardiotoxin

Genotype
MGI:6151150

cn11

• Allelic Composition: Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

mortality/aging

premature death ( J:260012 )

• all mice die between 3 weeks of age and P30

cardiovascular system

decreased myocardial fiber number ( J:260012 )

cardiac muscle necrosis ( J:260012 )

• focal with reduced cytoplasmic contents and vacuole formation

enlarged heart ( J:260012 )

increased heart weight ( J:260012 )

decreased cardiac muscle contractility ( J:260012 )

irregular heartbeat ( J:260012 )

prolonged QT interval ( J:260012 )

cardiomyopathy ( J:260012 )

muscle

muscle phenotype ( J:260012 )

N • muscles appear normal

decreased myocardial fiber number ( J:260012 )

cardiac muscle necrosis ( J:260012 )

• focal with reduced cytoplasmic contents and vacuole formation

decreased cardiac muscle contractility ( J:260012 )

cardiomyopathy ( J:260012 )

cellular

cardiac muscle necrosis ( J:260012 )

• focal with reduced cytoplasmic contents and vacuole formation

growth/size/body

enlarged heart ( J:260012 )

increased heart weight ( J:260012 )

Genotype
MGI:3721144

cn12

• Allelic Composition: Prkci^tm1Rfar/Prkci^tm1Rfar; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

homeostasis/metabolism

increased circulating leptin level ( J:123964 )

abnormal circulating lipid level ( J:123964 )

• males and females have more serum lipid than wild-type mice

decreased circulating HDL cholesterol level ( J:123964 )

increased circulating cholesterol level ( J:123964 )

increased circulating LDL cholesterol level ( J:123964 )

increased circulating free fatty acids level ( J:123964 )

• serum free fatty acid levels are increased by 40% relative to wild-type mice

increased circulating triglyceride level ( J:123964 )

• fasting triglyceride levels are increased relative to in wild-type mice

abnormal glucose homeostasis ( J:123964 )

• in a euglycemic clamp assay, mice require a reduced rate of glucose infusion compared to wild-type mice to maintain euglycemia

increased circulating glucose level ( J:123964 )

• in mice fed ad libitum, serum glucose levels are increased

• circulating glucose levels are higher in males than in females

increased circulating insulin level ( J:123964 )

• circulating insulin levels are higher in males than in females

impaired glucose tolerance ( J:123964 )

• in mice fed ad libitum, glucose tolerance impairment is comparable to or less severe than in heterozygotes

insulin resistance ( J:123964 )

• in mice fed ad libitum, insulin tolerance is impairment

• in a euglycemic clamp assay, whole-body insulin resistance is accounted for by decreases in insulin-stimulated whole-body glucose uptake and muscle glucose uptake of 25% and 30%, respectively

cardiovascular system

decreased cardiac muscle cell glucose uptake ( J:123964 )

• glucose uptake in heart muscle, basally and during insulin treatment, is reduced

muscle

decreased muscle cell glucose uptake ( J:123964 )

• glucose uptake in muscle (vastus laterallis and heart), basally and during insulin treatment, is reduced

• insulin-stimulated [³H]2-deoxyglucose uptake is reduced in slow-twitch (soleus) and fast-twitch (extensor digitorum longus) muscles

decreased cardiac muscle cell glucose uptake ( J:123964 )

• glucose uptake in heart muscle, basally and during insulin treatment, is reduced

liver/biliary system

hepatic steatosis ( J:123964 )

• even on a low-fat diet, hepatostetosis occurs and is more pronounced in heterogyzotes than in homozygotes

adipose tissue

decreased adipocyte glucose uptake ( J:123964 )

• insulin-stimulated glucose transport is impaired

growth/size/body

increased body weight ( J:123964 )

• body weight is increased relative to wild-type mice but is less than for heterozygous mice

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:123964 )

cellular

decreased adipocyte glucose uptake ( J:123964 )

• insulin-stimulated glucose transport is impaired

decreased muscle cell glucose uptake ( J:123964 )

• glucose uptake in muscle (vastus laterallis and heart), basally and during insulin treatment, is reduced

• insulin-stimulated [³H]2-deoxyglucose uptake is reduced in slow-twitch (soleus) and fast-twitch (extensor digitorum longus) muscles

decreased cardiac muscle cell glucose uptake ( J:123964 )

• glucose uptake in heart muscle, basally and during insulin treatment, is reduced

Genotype
MGI:3721145

cn13

• Allelic Composition: Prkci^tm1Rfar/Prkci⁺; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

homeostasis/metabolism

increased circulating leptin level ( J:123964 )

abnormal circulating lipid level ( J:123964 )

• males and females have more serum lipid than wild-type mice

decreased circulating HDL cholesterol level ( J:123964 )

increased circulating cholesterol level ( J:123964 )

increased circulating LDL cholesterol level ( J:123964 )

increased circulating free fatty acids level ( J:123964 )

• serum free fatty acid levels are increased by 90% relative to wild-type mice

increased circulating triglyceride level ( J:123964 )

• fasting triglyceride levels are increased relative to in wild-type mice

abnormal glucose homeostasis ( J:123964 )

• in a euglycemic clamp assay, mice require a reduced rate of glucose infusion compared to wild-type mice to maintain euglycemia

increased circulating glucose level ( J:123964 )

• in mice fed ad libitum, serum glucose levels are increased

• fasting glucose levels during insulin and glucose tolerance tests is increased by 20% to 25%

• when dietary fat content is increased from 5% to 10% for 2 months, mice exhibit higher glucose levels than in wild-type mice at all time points and during fasting glucose tolerance testing

increased circulating insulin level ( J:123964 )

• in mice fed ad libitum, serum insulin levels are increased

impaired glucose tolerance ( J:123964 )

• in mice fed ad libitum, glucose tolerance impairment is comparable to or more severe than in homozygotes

insulin resistance ( J:123964 )

• in mice fed ad libitum, insulin tolerance is impairment is comparable to or more severe than in homozygotes

• in a euglycemic clamp assay, whole-body insulin resistance is accounted for by decreases in insulin-stimulated whole-body glucose uptake and muscle glucose uptake of 25% and 30%, respectively

cardiovascular system

decreased cardiac muscle cell glucose uptake ( J:123964 )

muscle

decreased muscle cell glucose uptake ( J:123964 )

• insulin-stimulated uptake of glucose and [³H]2-deoxyglucose in vastus laterallis, soleus and extensor digitorum longus, and heart muscles is reduced by 50% to 60% compared to in wild-type mice

decreased cardiac muscle cell glucose uptake ( J:123964 )

liver/biliary system

hepatic steatosis ( J:123964 )

• even on a low-fat diet, hepatostetosis occurs and is more pronounced in heterogyzotes than in homozygotes

adipose tissue

decreased adipocyte glucose uptake ( J:123964 )

• insulin-stimulated glucose transport is impaired

growth/size/body

increased body weight ( J:123964 )

• body weight is increased relative to wild-type mice and homozygous mice

obese ( J:123964 )

• mice develop an obesity/diabetes syndrome associated with increased food intake

behavior/neurological

increased food intake ( J:123964 )

• mice consume 20% more regular chow than wild-type mice

immune system

increased susceptibility to autoimmune diabetes ( J:123964 )

• mice develop an obesity/diabetes syndrome associated with increased food intake

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:123964 )

cellular

decreased adipocyte glucose uptake ( J:123964 )

• insulin-stimulated glucose transport is impaired

decreased muscle cell glucose uptake ( J:123964 )

• insulin-stimulated uptake of glucose and [³H]2-deoxyglucose in vastus laterallis, soleus and extensor digitorum longus, and heart muscles is reduced by 50% to 60% compared to in wild-type mice

decreased cardiac muscle cell glucose uptake ( J:123964 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome		DOID:0060611	OMIM:PS605552	J:123964
obesity		DOID:9970	OMIM:601665	J:123964
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:123964

Genotype
MGI:5502413

cn14

• Allelic Composition: Abhd5^tm1Rze/Abhd5^tm1Rze; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

growth/size/body

increased heart weight ( J:197835 )

• 1.6-fold

mortality/aging

premature death ( J:197835 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:197835 )

N • mitochondrial fatty acid oxidation and triglyceride hydrolutic activities in skeletal muscle are normal

N • mice exhibit normal insulin sensitivity

decreased oxygen consumption ( J:197835 )

• in cardiac muscle

increased respiratory quotient ( J:197835 )

• during the light and dark phase

abnormal glucose homeostasis ( J:197835 )

• glucose clearance is enhanced

decreased circulating glucose level ( J:197835 )

• in fasted mice

• in re-fed mice

decreased circulating insulin level ( J:197835 )

• in re-fed mice

improved glucose tolerance ( J:197835 )

abnormal lipid homeostasis ( J:197835 )

• exercised mice fail to exhibit a decrease in the skeletal muscle indicating a defect in skeletal muscle triglyceride catabolism compared with control mice

increased cardiac muscle triglyceride level ( J:197835 )

• 43-fold in the cardiac muscle of non-fasted mice

• 15-fold in the cardiac muscle of fasted mice

decreased circulating free fatty acids level ( J:197835 )

• in non-exercised and exercised mice

decreased circulating triglyceride level ( J:197835 )

• in exercised mice

decreased liver triglyceride level ( J:197835 )

• moderate in fasted mice

increased skeletal muscle triglyceride level ( J:197835 )

• marked accumulation of triglycerides in skeletal muscle

• exercised mice fail to exhibit a decrease in skeletal muscle compared with control mice

impaired lipolysis ( J:197835 )

• in cardiac muscle

• however, in vitro triglyceride hydrolytic activity in skeletal muscle is normal

decreased lipoprotein lipase activity ( J:197835 )

• mild increase in LPA acyltransferase activity

cardiovascular system

increased cardiac muscle triglyceride level ( J:197835 )

• 43-fold in the cardiac muscle of non-fasted mice

• 15-fold in the cardiac muscle of fasted mice

myocardium steatosis ( J:197835 )

increased heart weight ( J:197835 )

• 1.6-fold

abnormal heart left ventricle morphology ( J:197835 )

• septal and posterial wall thickening

increased heart left ventricle weight ( J:197835 )

increased cardiac muscle cell glucose uptake ( J:197835 )

• increased 6.7-fold

• however, glucose uptake in skeletal muscle, liver and adipose tissue is normal

decreased ventricle muscle contractility ( J:197835 )

• left ventricle

muscle

increased cardiac muscle triglyceride level ( J:197835 )

• 43-fold in the cardiac muscle of non-fasted mice

• 15-fold in the cardiac muscle of fasted mice

myocardium steatosis ( J:197835 )

increased cardiac muscle cell glucose uptake ( J:197835 )

• increased 6.7-fold

• however, glucose uptake in skeletal muscle, liver and adipose tissue is normal

decreased ventricle muscle contractility ( J:197835 )

• left ventricle

increased skeletal muscle triglyceride level ( J:197835 )

• marked accumulation of triglycerides in skeletal muscle

• exercised mice fail to exhibit a decrease in skeletal muscle compared with control mice

liver/biliary system

decreased liver triglyceride level ( J:197835 )

• moderate in fasted mice

cellular

increased cardiac muscle cell glucose uptake ( J:197835 )

• increased 6.7-fold

• however, glucose uptake in skeletal muscle, liver and adipose tissue is normal

Genotype
MGI:5618526

cn15

• Allelic Composition: Slc7a5^tm1.1Daca/Slc7a5^tm1.1Daca; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

adipose tissue

increased gonadal fat pad weight ( J:213820 )

• increased gonadal fat mass

homeostasis/metabolism

abnormal amino acid level ( J:213820 )

• fasting results in no reduction in intramuscular concentrations of leucine and glutamine as compared to fasted wild-type mice

• intramuscular leucine concentration is not increased after leucine injection

• intramuscular leucine and isoleucine concentrations are increased in relation to increase in dietary protein; in wild-type mice concentrations remain the same

• plasma leucine concentration is unchanged in response to increases in dietary protein

• on a 30% protein diet, leucine, isoleucine and glutamine accumulate at higher levels in muscle relative to wild-type

insulin resistance ( J:213820 )

• mice fed 10%, 20% and 30% protein diets do not exhibit a graded increase in insulin sensitivity as compare to wild-type mice on the same diets

• plasma insulin levels are not significantly different from wild-type in fed state

Genotype
MGI:3800798

cn16

• Allelic Composition: Plec^tm4Gwi/Plec^tm4Gwi; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB

mortality/aging

decreased survivor rate ( J:137067 )

• decreased survival rates starting at 6 months of age

muscle

muscle phenotype ( J:137067 )

N • no abnormal muscle phenotype in early months of life

N • extensor digitorum longus is normal at 16 months of age

abnormal myocardial fiber morphology ( J:137067 )

• focal disorganization of contractile apparatus

abnormal muscle fiber mitochondrial morphology ( J:137067 )

• mitochondria lose association with Z-discs of muscle fibers

• mitochondria found in focal aggregates in sarcoplasm and subsarcolemmal regions

• numbers of mitochondria in muscle fibers is reduced

abnormal soleus morphology ( J:137067 )

• soleus muscle appears pale at 8 weeks of age and pathological changes are seen at 6 months

abnormal sarcolemma morphology ( J:137067 )

• detached from the contractile apparatus in the soleus and the diaphragm

• 61% of fibers with focal detachments at 8 weeks

abnormal skeletal muscle fiber morphology ( J:137067 )

• inner structure of fibers disorganized

• eosinophylic inclusions under the sarcolemma

skeletal muscle fiber necrosis ( J:137067 )

• numerous necrotic fibers in the soleus at 8 weeks

increased skeletal muscle fiber size ( J:137067 )

• hypertrophic and split fibers in both the soleus and diaphragm in older mice

centrally nucleated skeletal muscle fibers ( J:137067 )

• numerous centrally nucleated fibers in the soleus at 8 weeks

• at 3 months, 35% of fibers in exercised mice are centrally nucleated (45% at 12 months)

decreased skeletal muscle fiber number ( J:137067 )

• slight reduction in total number of fibers

decreased skeletal muscle mass ( J:137067 )

• loss of muscle mass observed in some mice at 16 months of age

skeletal muscle fiber atrophy ( J:137067 )

• atrophic fibers in soleus at 1 year

cardiovascular system

cardiovascular system phenotype ( J:137067 )

N • no heart pathologies at 12 months

N • no dilated or hypertrophic cardiomyopathies at 16 months of age

abnormal heart morphology ( J:137067 )

• increased connective tissue at 16 months of age

abnormal myocardial fiber morphology ( J:137067 )

• focal disorganization of contractile apparatus

cellular

abnormal muscle fiber mitochondrial morphology ( J:137067 )

• mitochondria lose association with Z-discs of muscle fibers

• mitochondria found in focal aggregates in sarcoplasm and subsarcolemmal regions

• numbers of mitochondria in muscle fibers is reduced

skeletal muscle fiber necrosis ( J:137067 )

• numerous necrotic fibers in the soleus at 8 weeks

homeostasis/metabolism

impaired exercise endurance ( J:137067 )

• decreased endurance during voluntary wheel running

behavior/neurological

impaired exercise endurance ( J:137067 )

• decreased endurance during voluntary wheel running

limbs/digits/tail

abnormal soleus morphology ( J:137067 )

• soleus muscle appears pale at 8 weeks of age and pathological changes are seen at 6 months

Genotype
MGI:6151152

cn17

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj * FVB

homeostasis/metabolism

abnormal autophagosome formation ( J:260012 )

• impaired autophagosome formation

mortality/aging

premature death ( J:260012 )

• mice survive to 7 weeks after birth

cardiovascular system

cardiovascular system phenotype ( J:260012 )

N • mice exhibit normal heart weight, cardiac contractility and QT interval

cellular

abnormal autophagosome formation ( J:260012 )

• impaired autophagosome formation

Genotype
MGI:3843872

cn18

• Allelic Composition: Pdha1^tm1Ptl/Pdha1⁺; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

cardiovascular system

increased myocardial fiber size ( J:141289 )

♀

increased heart weight ( J:141289 )

♀ • mice exhibit increased heart weight compared to in wild-type mice

♀ • however, heart weight to body weight is normal

abnormal heart left ventricle morphology ( J:141289 )

♀ • when mice are transitioned from a high fat diet to a rodent laboratory diet, the left ventricular diastolic dimension is increased compared to in wild-type mice

decreased cardiac muscle contractility ( J:141289 )

♀ • when transitioned from a high fat diet to a rodent laboratory diet, mice exhibit reduced fractional shortening compared to in wild-type mice

growth/size/body

increased heart weight ( J:141289 )

♀ • mice exhibit increased heart weight compared to in wild-type mice

♀ • however, heart weight to body weight is normal

increased body weight ( J:141289 )

♀ • at 9 weeks of age

homeostasis/metabolism

increased circulating insulin level ( J:141289 )

♀

muscle

increased myocardial fiber size ( J:141289 )

♀

decreased cardiac muscle contractility ( J:141289 )

♀ • when transitioned from a high fat diet to a rodent laboratory diet, mice exhibit reduced fractional shortening compared to in wild-type mice

Genotype
MGI:3843870

cn19

• Allelic Composition: Pdha1^tm1Ptl/Y; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

mortality/aging

premature death ( J:141289 )

♂ • when weaned onto rodent laboratory chow, male mice die 7 days after weaning

♂ • when mice are weaned onto a high fat diet, male mice die 12 days after switching from a high fat diet to rodent laboratory chow

cardiovascular system

increased myocardial fiber size ( J:141289 )

♂ • compared to in heterozygous female mice and wild-type mice

increased heart weight ( J:141289 )

♂

abnormal heart left ventricle morphology ( J:141289 )

♂ • whether mice are fed a high fat or laboratory chow diet, the left ventricular diastolic dimension is increased compared to in wild-type mice

heart left ventricle hypertrophy ( J:141289 )

♂

decreased cardiac muscle contractility ( J:141289 )

♂ • whether fed a high fat or laboratory chow diet, mice exhibit reduced fractional shortening compared to in heterozygous female mice and wild-type mice

homeostasis/metabolism

increased circulating insulin level ( J:141289 )

♂

growth/size/body

heart left ventricle hypertrophy ( J:141289 )

♂

increased heart weight ( J:141289 )

♂

increased body weight ( J:141289 )

♂ • at 9 weeks of age

muscle

increased myocardial fiber size ( J:141289 )

♂ • compared to in heterozygous female mice and wild-type mice

heart left ventricle hypertrophy ( J:141289 )

♂

decreased cardiac muscle contractility ( J:141289 )

♂ • whether fed a high fat or laboratory chow diet, mice exhibit reduced fractional shortening compared to in heterozygous female mice and wild-type mice

Genotype
MGI:4462798

cn20

• Allelic Composition: Glul^tm3Whla/Glul^tm1Whla; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

homeostasis/metabolism

abnormal amino acid level ( J:161082 )

• 35% increase in branched-chain amino acids

decreased glutamine level ( J:161082 )

• muscle glutamine 20-30% lower

decreased circulating glutamine level ( J:161082 )

• 20% reduction in plasma glutamine in starved mice

abnormal ammonia homeostasis ( J:161082 )

• detoxification of ammonia is two fold lower

growth/size/body

abnormal postnatal growth ( J:161082 )

• faster weight loss when fasting but only for the first 20 hours

Genotype
MGI:3619942

cn21

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Tg(Ckmm-cre)5Khn/0; Tg(Myh6-Pik3ca)1Siz/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

cardiovascular system

small heart ( J:79151 )

• display a reduction in heart size similar to that seen in single Tg(Myh6-Pik3ca)1Siz mice

decreased cardiac muscle contractility ( J:79151 )

muscle

decreased cardiac muscle contractility ( J:79151 )

Genotype
MGI:3619937

cn22

• Allelic Composition: Pik3cg^tm1Pngr/Pik3cg^tm1Pngr; Pten^tm2Mak/Pten^tm2Mak; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

cardiovascular system

enlarged heart ( J:79151 )

• significantly enlarged compared to wild-type and single homozygous Pik3cg^tm1Pngr mice

cardiac hypertrophy ( J:79151 )

• extent of cardiac hypertrophy is similar to that seen in mice with cardiomyocyte-specific inactivation of Pten

increased cardiac muscle contractility ( J:79151 )

• hearts are hypercontractile as assessed by increased fractional shortening, velocity or circumferential fiber shortening, and peak aortic outflow velocity

• individual cardiomyocytes display increased contractility despite the hypertrophy

muscle

increased cardiac muscle contractility ( J:79151 )

• hearts are hypercontractile as assessed by increased fractional shortening, velocity or circumferential fiber shortening, and peak aortic outflow velocity

• individual cardiomyocytes display increased contractility despite the hypertrophy

growth/size/body

enlarged heart ( J:79151 )

• significantly enlarged compared to wild-type and single homozygous Pik3cg^tm1Pngr mice

cardiac hypertrophy ( J:79151 )

• extent of cardiac hypertrophy is similar to that seen in mice with cardiomyocyte-specific inactivation of Pten

Genotype
MGI:3687267

cn23

• Allelic Composition: Aifm1^tm2Pngr/Y; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

growth/size/body

enlarged heart ( J:113016 )

♂ • mice have grossly enlarged hearts at 9 weeks of age

cardiac hypertrophy ( J:113016 )

♂ • 9-week old mice show significant increase in heart weight/tibial-length ratios

weight loss ( J:113016 )

♂ • male mutants appear normal at 2 months; at 3 months, they display significant weight loss

cellular

abnormal mitochondrial morphology ( J:113016 )

♂ • mitochondria display abnormal morphology at 9 weeks but not at 4 weeks of age

abnormal mitochondrial crista morphology ( J:113016 )

• mitochondria display marked cristolysis at 9 weeks but not at 4 weeks of age

increased mitochondrial number ( J:113016 )

♂ • heart muscle has increased number of mitochondria

abnormal aerobic respiration ( J:113016 )

♂ • lipid peroxidation markers are increased >2.5 fold in 9-week old mutants indicating impaired mitochondrial respiration

abnormal mitochondrial physiology ( J:113016 )

♂ • a significant increase in lactate/pyruvate ratio is observed

abnormal respiratory electron transport chain ( J:113016 )

♂ • complex I respiratory chain complex is reduced to ~50% of control levels in heart and gastrocnemius at 5 weeks of age, while complex III level is ~90% of control in heart and gastrocnemius

abnormal mitochondrial ATP synthesis coupled electron transport ( J:113016 )

♂ • respiratory chain enzyme activities in soleus, gastrocnemium and heart muscle is severely reduced; complex I activity in skeletal muscle and heart is reduced (up to 80%) while complex IV activity in the heart is more mildly reduced at 18 weeks of age

oxidative stress ( J:113016 )

♂ • lipid peroxidation markers (indicators or oxidative stress) are increased >2.5 fold in 9-week old mutants

cardiovascular system

abnormal myocardial fiber morphology ( J:113016 )

♂ • heart muscle shows pronounced myofibrillar fragmentation and disorganization and increased number of mitochondria

increased myocardial fiber size ( J:113016 )

♂ • individual cardiomyocytes are markedly increased in size

enlarged heart ( J:113016 )

♂ • mice have grossly enlarged hearts at 9 weeks of age

cardiac hypertrophy ( J:113016 )

♂ • 9-week old mice show significant increase in heart weight/tibial-length ratios

dilated cardiomyopathy ( J:113016 )

♂ • mutants display severe dilated cardiomyopathy

decreased cardiac muscle contractility ( J:113016 )

♂ • detectable by 4 weeks of age and progressively worsens

♂ • significant decrease is shown by decreased percentage fractional shortening, decreased velocity of circumferential fiber shortening and reduced peak aortic outlflow velocity

♂ • also, dP/dT_max and dP/dT_min are reduced significantly

abnormal heart ventricle pressure ( J:113016 )

♂ • mutants have significant decrease in ventricular blood pressures

muscle

abnormal myocardial fiber morphology ( J:113016 )

♂ • heart muscle shows pronounced myofibrillar fragmentation and disorganization and increased number of mitochondria

increased myocardial fiber size ( J:113016 )

♂ • individual cardiomyocytes are markedly increased in size

dilated cardiomyopathy ( J:113016 )

♂ • mutants display severe dilated cardiomyopathy

decreased cardiac muscle contractility ( J:113016 )

♂ • detectable by 4 weeks of age and progressively worsens

♂ • significant decrease is shown by decreased percentage fractional shortening, decreased velocity of circumferential fiber shortening and reduced peak aortic outlflow velocity

♂ • also, dP/dT_max and dP/dT_min are reduced significantly

abnormal skeletal muscle fiber morphology ( J:113016 )

♂ • myofibers from 3-month old mice display irregular contours

increased skeletal muscle fiber diameter ( J:113016 )

♂ • myofiber cross-sectional area is reduced 2-fold in triceps of 3 month old mice vs littermate controls

decreased skeletal muscle mass ( J:113016 )

♂ • male hemizygotes display significant loss of muscle mass at 3 months, becoming detectable at 10 weeks of age compared to littermate controls (Pdcd8-sufficent and non-transgenic hemizygotes)

muscle degeneration ( J:113016 )

♂ • muscle degeneration is progressive, becoming detectable at 10 weeks of age; it is most apparent in fast-twitch muscles (gastrocnemium, triceps, quadriceps)

muscular atrophy ( J:113016 )

♂ • all skeletal muscles analyzed including triceps, pectoralis, quadriceps, gluteus, and gastrocnemius muscles are significantly atrophied male hemizygotes

homeostasis/metabolism

increased circulating lactate level ( J:113016 )

♂ • plasma lactate levels increase progressively with muscle loss

♂ • a significant increase in lactate/pyruvate ratio is observed

abnormal glucose homeostasis ( J:113016 )

♂ • mutant cardiomyocytes undergo compensatory metabolic switch toward glycolysis, and away from pyruvate utilization as result of impaired mitochondrial respiration

abnormal hormone level ( J:113016 )

♂ • mutants show significant upregulation of atrial naturietic factor (ANF) and b-type natruietic peptide (BNP)

decreased catalase activity ( J:113016 )

♂ • at 4.5 months of age, heart and skeletal muscle show significant reductions in catalase activity

behavior/neurological

lethargy ( J:113016 )

♂ • loss of muscle mass results makes mice extremely lethargic by 5 months of age

Genotype
MGI:3619927

cn24

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

cardiovascular system

abnormal heart morphology ( J:79151 )

• exhibit an increase in the anterior wall thickness, however see no evidence of wall thinning or tissue fibrosis and heart rate is normal

increased myocardial fiber size ( J:79151 )

• increase in both the length and width of cardiomyocytes

enlarged heart ( J:79151 )

• increased in heart size is detectable in newborns

cardiac hypertrophy ( J:79151 )

• seen at 10 weeks and 12 months of age, however do not observe cardiac decompensation or dilated cardiomyopathy

abnormal heart left ventricle morphology ( J:79151 )

• exhibit an increase in the left ventricle mass

decreased cardiac muscle contractility ( J:79151 )

• decrease in fractional shortening, velocity of circumferential fiber shortening, peak aortic outflow velocity, dP/dT-max and dP/dT-min, indicating impaired contractile heart function

• individual cardiomyocytes display a reduction in contractility as shown by a reduction in percent cell shortening and positive and negative dL/dTs

muscle

increased myocardial fiber size ( J:79151 )

• increase in both the length and width of cardiomyocytes

decreased cardiac muscle contractility ( J:79151 )

• decrease in fractional shortening, velocity of circumferential fiber shortening, peak aortic outflow velocity, dP/dT-max and dP/dT-min, indicating impaired contractile heart function

• individual cardiomyocytes display a reduction in contractility as shown by a reduction in percent cell shortening and positive and negative dL/dTs

growth/size/body

enlarged heart ( J:79151 )

• increased in heart size is detectable in newborns

cardiac hypertrophy ( J:79151 )

• seen at 10 weeks and 12 months of age, however do not observe cardiac decompensation or dilated cardiomyopathy

Genotype
MGI:4462799

cn25

• Allelic Composition: Glul^tm3Whla/Glul^tm3Whla; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

growth/size/body

abnormal postnatal growth ( J:161082 )

• faster weight loss when fasting but only for the first 20 hours

homeostasis/metabolism

abnormal amino acid level ( J:161082 )

• 20% reduction in plasma glutamine in starved mice

• muscle glutamine20-30% lower

• 35% increase in branched-chain amino acids

abnormal ion homeostasis ( J:161082 )

• detoxification of ammonia is two fold lower

Genotype
MGI:6280693

cn26

• Allelic Composition: Parl^tm1Bdes/Parl^tm1Bdes; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

mortality/aging

mortality/aging ( J:269785 )

N • mice exhibit normal survival

behavior/neurological

behavior/neurological phenotype ( J:269785 )

N • mice exhibit normal locomotor skills

Genotype
MGI:6458049

cn27

• Allelic Composition: Lama2^tm1Eeng/Lama2^tm1Eeng; Smdt1^{tm1c(EUCOMM)Wtsi}/Smdt1^{tm1c(EUCOMM)Wtsi}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6N * FVB

mortality/aging

premature death ( J:287405 )

• as in Lama2^tm1Eeng homozygotes

behavior/neurological

decreased grip strength ( J:287405 )

• as in Lama2^tm1Eeng homozygotes

cellular

abnormal mitochondrial physiology ( J:287405 )

• increase in mitochondrial calcium in skeletal muscle fiber as in Lama2^tm1Eeng homozygotes

Genotype
MGI:2449942

cn28

• Allelic Composition: Erbb2^{tm3(Erbb2)Mul}/Erbb2^{tm3(Erbb2)Mul}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * FVB

mortality/aging

premature death ( J:81565 )

• early mortality is observed in severely affected mutants

behavior/neurological

impaired coordination ( J:81565 )

• loss of coordination

impaired limb coordination ( J:81565 )

abnormal posture ( J:81565 )

• progressive with age, animals rest on abdomen instead of limbs

abnormal limb posture ( J:81565 )

• mutants often maintain limbs in an abnormal posture, progressing from a flexor to an extensor posture

abnormal gait ( J:81565 )

• progressive with age

craniofacial

malocclusion ( J:81565 )

growth/size/body

malocclusion ( J:81565 )

cachexia ( J:81565 )

muscle

increased myoblast apoptosis ( J:81565 )

• an increase in apoptosis is observed in mutant myoblasts infected with adenoviral-cre (to completely obliterate expression) during induced differentiation

absent primary muscle spindle ( J:81565 )

absent secondary muscle spindle ( J:81565 )

impaired skeletal muscle regeneration ( J:81565 )

• 2 weeks after a muscle crush injury in the tibialis anterior, muscle fibers that have regenerated are not continuous and are interspersed with encapsulated cellular debris

skeleton

malocclusion ( J:81565 )

nervous system

absent primary muscle spindle ( J:81565 )

absent secondary muscle spindle ( J:81565 )

cellular

increased myoblast apoptosis ( J:81565 )

• an increase in apoptosis is observed in mutant myoblasts infected with adenoviral-cre (to completely obliterate expression) during induced differentiation

Genotype
MGI:5292478

cn29

• Allelic Composition: Mterf4^tm1.1Lrsn/Mterf4^tm1.1Lrsn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB

mortality/aging

premature death ( J:175816 )

• maximal life span is shortened to 21 weeks

cardiovascular system

abnormal myocardial fiber morphology ( J:175816 )

• gradual accumulation of mitochondria with abnormal morphology in the myocardium from 5 weeks of age onwards

enlarged heart ( J:175816 )

• gradual increase in absolute and relative heart size with age

abnormal myocardial fiber physiology ( J:175816 )

• levels of assembled complexes containing mtDNA-encoded subunits are decreased from 5 weeks of age onward

• severe respiratory chain deficiency

cardiomyopathy ( J:175816 )

• severe mitochondrial cardiomyopathy develops from 5 weeks of age onwards

cellular

abnormal mitochondrial physiology ( J:175816 )

• severe decrease of in organello translation in the hearts

growth/size/body

enlarged heart ( J:175816 )

• gradual increase in absolute and relative heart size with age

decreased body weight ( J:175816 )

• from 15 weeks of age

muscle

abnormal myocardial fiber morphology ( J:175816 )

• gradual accumulation of mitochondria with abnormal morphology in the myocardium from 5 weeks of age onwards

cardiomyopathy ( J:175816 )

• severe mitochondrial cardiomyopathy develops from 5 weeks of age onwards

Genotype
MGI:3839275

cn30

• Allelic Composition: Mterf3^tm1.1Lrsn/Mterf3^tm1.1Lrsn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB * SJL

mortality/aging

premature death ( J:145125 )

• mice die by 18 weeks of age

cardiovascular system

abnormal myocardial fiber morphology ( J:145125 )

• mice exhibit an increase in relative mitochondrial mass in hearts unlike in wild-type mice

enlarged heart ( J:145125 )

• mice exhibit a gradual increase in heart size with abnormal mitochondria unlike in wild-type mice

cardiomyopathy ( J:145125 )

• mitochondrial

cellular

abnormal mitochondrial physiology ( J:145125 )

• steady-state mitochondrial transcription is decreased compared to in wild-type cells

abnormal mitochondrial ATP synthesis coupled electron transport ( J:145125 )

• the enzymatic activity of all mitochondrial complexes in heart tissues is decreased compared to in wild-type mice

growth/size/body

enlarged heart ( J:145125 )

• mice exhibit a gradual increase in heart size with abnormal mitochondria unlike in wild-type mice

decreased body weight ( J:145125 )

• at 16 weeks of age

muscle

abnormal myocardial fiber morphology ( J:145125 )

• mice exhibit an increase in relative mitochondrial mass in hearts unlike in wild-type mice

cardiomyopathy ( J:145125 )

• mitochondrial

Genotype
MGI:3844252

cn31

• Allelic Composition: Tfb1m^tm1.1Lrsn/Tfb1m^tm1.1Lrsn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB * SJL

mortality/aging

premature death ( J:148166 )

• at 24 weeks of age

cardiovascular system

abnormal myocardial fiber morphology ( J:148166 )

• after 10 weeks, mitochondrial mass in cardiomyocytes increases unlike in wild-type mice

increased heart weight ( J:148166 )

• after 15 weeks

abnormal myocardial fiber physiology ( J:148166 )

• at 15 to 20 weeks, mitochondrial biogenesis in cardiomyocytes is increased compared to in wild-type mice

• at 5 and 20 weeks, respiratory function and mitochondrial ATP production is decreased compared to in wild-type cells

• heart cells exhibit increased mitochondrial transcription but decreased translation compared to in wild-type cells

muscle

abnormal myocardial fiber morphology ( J:148166 )

• after 10 weeks, mitochondrial mass in cardiomyocytes increases unlike in wild-type mice

growth/size/body

increased heart weight ( J:148166 )

• after 15 weeks

Genotype
MGI:3621470

cn32

• Allelic Composition: Hif1a^tm3Rsjo/Hif1a^tm3Rsjo; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

muscle

abnormal muscle physiology ( J:97761 )

• increase in muscle damage following exercise

homeostasis/metabolism

increased circulating creatine kinase level ( J:97761 )

• increased serum levels of the MM isoform of creatine kinase 1 day after exercise

abnormal glucose homeostasis ( J:97761 )

• significant decrease in lactate accumulation after exercise

abnormal exercise endurance ( J:97761 )

• increased endurance in swim tests and in the first session of running uphill (concentric exercise) but decreased endurance when running downhill (eccentric exercise)

• endurance decreased over 4 consecutive days of daily treadmill running

nervous system

abnormal innervation pattern to muscle ( J:97761 )

• slight but statistically significant decrease in type IIa fibers in the soleus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glycogen storage disease V		DOID:2746	OMIM:232600	J:97761
glycogen storage disease VII		DOID:11721	OMIM:232800	J:97761

Genotype
MGI:2661075

cn33

• Allelic Composition: Mstn^tm1Mgs/Mstn^tm1Mgs; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1 * FVB

growth/size/body

increased body weight ( J:83122 )

• mutants weigh 23% and 26% more than controls at 2 months and 5 months of age, respectively

muscle

abnormal muscle morphology ( J:83122 )

• generalized muscle hypertrophy, resulting in a 'double-muscling' phenotype

• superficial muscle layers exhibit a more severe hypertrophy than the deep layers

increased skeletal muscle fiber size ( J:83122 )

increased muscle weight ( J:83122 )

skeletal muscle hypertrophy ( J:83122 )

Genotype
MGI:2450243

cn34

• Allelic Composition: Dag1^tm2Kcam/Dag1^tm2Kcam; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

muscle

abnormal skeletal muscle morphology ( J:78838 )

• at ~6 weeks, mutant skeletal muscles show loss of dystrophin, dystrobrevin, and the sarcoglycan-sarcospan complex

• during cycles of degeneration, satellite cells are repetitively activated leading to expression of dystroglycan and other components of the DGC in muscle fibers undergoing regeneration

skeletal muscle necrosis ( J:78838 )

• at ~6 weeks, mutant skeletal muscles, including quadriceps, gastrocnemius, tibialis anterior, biceps, gluteus maximus, and diaphragm, display myonecrosis

increased skeletal muscle fiber size ( J:78838 )

• surprisingly, aging mutants develop marked hypertrophy of skeletal muscle fibers

increased skeletal muscle fiber diameter ( J:78838 )

• a >2-fold increase in fiber diameter of the quadriceps and soleus muscle noted at 18 months

increased variability of skeletal muscle fiber size ( J:78838 )

• at ~6 weeks, mutant mice show variation of skeletal muscle fiber size

centrally nucleated skeletal muscle fibers ( J:78838 )

• up to 95% of skeletal muscle fibers exhibit centrally located nuclei

increased skeletal muscle weight ( J:78838 )

• at 15 months, mutants show a widespread increase in wet muscle weight, esp. in the quadriceps and gastrocnemius muscles, where the weight is doubled

dystrophic muscle ( J:78838 )

• at ~6 weeks, mutants exhibit hallmarks of muscular dystrophy, such as myonecrosis, central nucleation, and variation of fiber size

• however, despite ongoing cycles of muscle degeneration, aging mutants exhibit only a mild dystrophy with signs of efficient muscle regeneration and marked skeletal muscle hypertrophy but no signs of fibrosis or fat replacement

homeostasis/metabolism

increased circulating creatine kinase level ( J:78838 )

• mutant mice exhibit significant elevation of serum creatine kinase levels

growth/size/body

increased body size ( J:78838 )

• at 15 months, mutant mice are significantly larger than control littermates

cellular

skeletal muscle necrosis ( J:78838 )

• at ~6 weeks, mutant skeletal muscles, including quadriceps, gastrocnemius, tibialis anterior, biceps, gluteus maximus, and diaphragm, display myonecrosis

Genotype
MGI:3722124

cn35

• Allelic Composition: Rr27^tm1Kpfe/Rr27^tm1Kpfe; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

cellular

abnormal imprinting ( J:82798 )

• maternal allele imprinting is lost

• however, imprinting at the H19 promoter in the paternal allele is normal

Genotype
MGI:5906203

cn36

• Allelic Composition: Ptpn11^tm1Gsf/Ptpn11^tm1Gsf; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

growth/size/body

enlarged heart ( J:144767 )

♂ • 66% increase in heart/body weight ratios

mortality/aging

premature death ( J:144767 )

• mice begin to die within 2 weeks after birth and have a median survival age of 13.4 weeks, with very few living up to 36 weeks

cardiovascular system

increased cardiac muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in the heart

• however, no differences in glycogen content of cardiac muscle

increased myocardial fiber size ( J:144767 )

♂ • cardiomyocyte capacitance, a measure of cell size, is augmented, with cells showing a 2-fold increase in capacitance

enlarged heart ( J:144767 )

♂ • 66% increase in heart/body weight ratios

increased heart ventricle size ( J:144767 )

♂

dilated cardiomyopathy ( J:144767 )

♂ • enlarged right and left ventricle chambers with thinner walls

♂ • however, fibrosis, changes in apoptosis or proliferation,or lymphocyte and macrophage infiltration in the heart are not seen

decreased cardiac muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in cardiac muscle cells

decreased ventricle muscle contractility ( J:144767 )

♂ • decrease in left ventricular fraction shortening and the velocity of circumferential fiber shortening

abnormal heart echocardiography feature ( J:144767 )

♂ • enlarged left ventricular chamber size in 6 week old mice, increase in left ventricular internal dimension at end diastole and end systole, and significant wall thinning as evidenced by decrease in systolic dimensions in interventricular septal wall thickness

♂ • however, no change in left ventricular posterior wall thickness is seen

abnormal myocardial fiber calcium currents ( J:144767 )

♂ • cardiomyocytes exhibit slower calcium current density (inward current amplitude normalized to cell capacitance)

congestive heart failure ( J:144767 )

♂

cellular

decreased muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in skeletal muscle cells

decreased cardiac muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in cardiac muscle cells

homeostasis/metabolism

increased cardiac muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in the heart

• however, no differences in glycogen content of cardiac muscle

increased circulating insulin level ( J:144767 )

♂ • circulating insulin levels under fed and fasted conditions are slightly increased

increased circulating triglyceride level ( J:144767 )

• elevation in levels of triglyceride in plasma

• however, no differences in circulating free fatty acids

impaired glucose tolerance ( J:144767 )

• glucose intolerance, with the most significant difference seen at 120 min after glucose injection

insulin resistance ( J:144767 )

• males and females show a decreased ability to lower circulating glucose levels after intraperitoneal injection of insulin

increased skeletal muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in skeletal muscle

• however, no differences in glycogen content of skeletal muscle

muscle

increased cardiac muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in the heart

• however, no differences in glycogen content of cardiac muscle

increased myocardial fiber size ( J:144767 )

♂ • cardiomyocyte capacitance, a measure of cell size, is augmented, with cells showing a 2-fold increase in capacitance

dilated cardiomyopathy ( J:144767 )

♂ • enlarged right and left ventricle chambers with thinner walls

♂ • however, fibrosis, changes in apoptosis or proliferation,or lymphocyte and macrophage infiltration in the heart are not seen

decreased ventricle muscle contractility ( J:144767 )

♂ • decrease in left ventricular fraction shortening and the velocity of circumferential fiber shortening

decreased muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in skeletal muscle cells

decreased cardiac muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in cardiac muscle cells

increased skeletal muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in skeletal muscle

• however, no differences in glycogen content of skeletal muscle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:144767
disease of metabolism		DOID:0014667		J:144767

Genotype
MGI:5438914

cn37

• Allelic Composition: Lrpprc^tm1.1Lrsn/Lrpprc^tm1.1Lrsn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

mortality/aging

premature death ( J:187800 )

• mice die before 16 weeks of age

cellular

increased mitochondrial DNA content ( J:187800 )

• increased mitochondrial DNA content

increased mitochondrial size ( J:187800 )

• increased mitochondrial mass associated with a severe cytochrome c oxidase deficiency

abnormal mitochondrial physiology ( J:187800 )

• severe cytochrome c oxidase deficiency

• aberrant polyadenyation of mitochondrial mRNA and impaired mRNA stability

cardiovascular system

enlarged heart ( J:187800 )

growth/size/body

enlarged heart ( J:187800 )

Genotype
MGI:6275157

cn38

• Allelic Composition: Esr1^tm4.2Ksk/Esr1^tm4.2Ksk; Mir22^tm1Boet/Mir22^tm1Boet; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB

homeostasis/metabolism

increased fatty acid oxidation ( J:266382 )

• mitochondrial in muscle cells

• however, muscle cells exhibit normal total and extramitochondrial fatty acid oxidation

adipose tissue

adipose tissue phenotype ( J:266382 )

N • mice exhibit normal fat amounts unlike mice homozygous for a knock-out allele of Mir22^tm1Boet

growth/size/body

growth/size/body region phenotype ( J:266382 )

N • male and female mice exhibit normal body weight

muscle

muscle phenotype ( J:266382 )

N • mice exhibit normal muscle fiber composition and mitochondrial content

cellular

increased fatty acid oxidation ( J:266382 )

• mitochondrial in muscle cells

• however, muscle cells exhibit normal total and extramitochondrial fatty acid oxidation

Genotype
MGI:5469974

cn39

• Allelic Composition: Scyl1^tm1Spel/Scyl1^tm1Spel; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB/N

behavior/neurological

behavior/neurological phenotype ( J:192445 )

N • mice exhibit normal gait and motor function

muscle

muscle phenotype ( J:192445 )

N • mice exhibit normal gait and motor function

nervous system

nervous system phenotype ( J:192445 )

N • mice exhibit nor signs of neuroinflammation or neurodegeneration

Genotype
MGI:3775309

cn40

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB

cardiovascular system

cardiovascular system phenotype ( J:118987 )

N • heart function and morphology is normal

growth/size/body

growth/size/body region phenotype ( J:118987 )

N • mice exhibit normal growth rates

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N • mice exhibit normal glucose homeostasis

Genotype
MGI:5494712

cn41

• Allelic Composition: Mapk8^tm1Jcbr/Mapk8^tm1Jcbr; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB

growth/size/body

growth/size/body region phenotype ( J:195844 )

N • whether fed standard chow or a high fat diet, mice exhibit normal body composition

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:195844 )

N • whether fed standard chow or a high fat diet, mice exhibit normal energy homeostasis, insulin sensitivity and glucose homeostasis

Genotype
MGI:4821347

cn42

• Allelic Composition: Dgcr8^tm1.1Blel/Dgcr8^tm1.1Blel; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB

mortality/aging

premature death ( J:161342 )

• all mice die before 2 months of age and median survival is 31 days

cardiovascular system

enlarged heart ( J:161342 )

abnormal heart ventricle morphology ( J:161342 )

• at 4 weeks, mice exhibit increased end-diastolic and end-systolic diameters compared with wild-type mice

thin ventricular wall ( J:161342 )

• in the left and right ventricular wall

cardiac fibrosis ( J:161342 )

• in the ventricular wall at 3 weeks

decreased ventricle muscle contractility ( J:161342 )

• at 3 weeks, mice exhibit loss of ventricular function unlike wild-type mice

• at 4 weeks, fractional shortening is reduced in the ventricle compared with wild-type mice

prolonged PR interval ( J:161342 )

prolonged QRS complex duration ( J:161342 )

• increased in width

muscle

decreased ventricle muscle contractility ( J:161342 )

• at 3 weeks, mice exhibit loss of ventricular function unlike wild-type mice

• at 4 weeks, fractional shortening is reduced in the ventricle compared with wild-type mice

growth/size/body

enlarged heart ( J:161342 )

Genotype
MGI:2389586

cn43

• Allelic Composition: Insr^tm1Khn/Insr^tm1Dac; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * FVB

homeostasis/metabolism

hyperglycemia ( J:51266 )

• in the fed state, incomplete penetrance

increased circulating insulin level ( J:51266 )

Genotype
MGI:2389585

cn44

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * FVB

adipose tissue

abnormal fat pad morphology ( J:51266 )

• larger than normal fat depots in fat pads, including the perianal, subcutaneous and perigonadal fat pads

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:51266 )

N • normal serum cholesterol levels

N • normoglycemia, up to 11 months of age

N • normal glucose tolerance

N • normal concentrations of serum insulin

increased fatty acids level ( J:51266 )

• 20% elevation in serum free fatty acids (FFAs)

increased triglyceride level ( J:51266 )

• greater than70% elevated, observed from ages 4 to 11 months

Genotype
MGI:5317893

cn45

• Allelic Composition: Akt1^tm2Mbb/Akt1^tm2Mbb; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * FVB

growth/size/body

growth/size/body region phenotype ( J:182721 )

N • mice do not phenocopy knock-out mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:182721 )

N • mice do not phenocopy knock-out mice

Genotype
MGI:6458047

cn46

• Allelic Composition: Smdt1^{tm1c(EUCOMM)Wtsi}/Smdt1^{tm1c(EUCOMM)Wtsi}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6N * FVB

cellular

abnormal mitochondrial physiology ( J:287405 )

• slight decrease in mitochondrial calcium in skeletal muscle fiber

growth/size/body

growth/size/body region phenotype ( J:287405 )

N • mice exhibit normal body weight

behavior/neurological

behavior/neurological phenotype ( J:287405 )

N • mice exhibit normal grip strength

Genotype
MGI:3663416

cn47

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4^tm1Abel; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * FVB

homeostasis/metabolism

abnormal glucose homeostasis ( J:110773 )

• during a 2 hour hyperinsulinemic-euglycemic clamp insulin-stimulated whole body glycolysis is reduced by 59% (49 umol/kg/min vs 118 umol/kg/min in 21-week old controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated whole body glycolysis is reduced by 43% (95 umol/kg/min vs 166 umol/kg/min in young controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated skeletal muscle glycolysis is reduced by 92% (18 nmol/g/min vs 223 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, whole body glycolysis is reduced by 30% (98 vs 118 umol/kg/min) and and muscle glycolysis is reduced by 82% (44 vs 251 nmol/g/min); hepatic glucose production is unaffected by insulin

• during a 2 hour hyperinsulinemic-euglycemic clamp inhibition of hepatic glucose production by mutants is impaired in 21-week old mutants

increased circulating glucose level ( J:110773 )

• basal plasma glucose concentration (8.2mM) is increased about 20% compared to controls (Slc2a4^tm1Abel homozygotes at 21 weeks of age or mice expressing Tg(Ckmm-cre)1Khan alone) where levels are 6.8-7.2 mM

• however, young (0-week old) muscle-specific knockouts showed no increased plasma glucose vs age-matched controls

• in young mutants treated from 12 weeks of age with phloridzin, plasma glucose levels show an initial increase (10.2 vs 6.7 mM in controls) but levels gradually decrease to comparable levels with controls (8.2, 6.9 and 7.0 mM vs 7.0 mM in controls at 14, 17 and 20 weeks of age)

increased circulating insulin level ( J:110773 )

• 21-week old knockout mice do not show differences in basal plasma insulin levels after an overnight fast, while levels are significantly increased in young (10-week old) knockouts (~110 pM vs 53 pM) and phloridzin treated knockouts compared to their respective controls (166 pM vs 86 pM)

abnormal lipid homeostasis ( J:110773 )

• during a 2 hour hyperinsulinemic-euglycemic clamp insulin-stimulated whole body glycogen/lipid synthesis is decreased by 50% in 21-week old knockouts

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated whole body glycogen/lipid synthesis is decreased by 60% (36 vs 90 umol/kg/min) compared to young controls

• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated skeletal muscle glycogen/lipid synthesis is decreased by 89% (0.7 vs 2.7 nmol/g/min) compared to young controls

• in young mutants treated from 12 weeks of age with phloridzin, whole body glycogen/lipid biosynthesis is decreased by 36% (44 vs 106 umol/kg/min) and muscle glycogen/lipid synthesis is reduced by 45% ( 4.7 vs 8.7 nmol/g/min)

muscle

decreased muscle cell glucose uptake ( J:110773 )

• uptake in skeletal (gastrocnemius) muscle is decreased by 92% in muscle-specific knockouts (20 vs 237 nmol/g/min in controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated uptake in skeletal muscle in 10-week old mutants is decreased by 85% (39 vs 261 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, skeletal muscle uptake is decreased by 81% (49 vs 227 nmol/g/min)

adipose tissue

decreased adipocyte glucose uptake ( J:110773 )

• insulin-stimulated glucose uptake in white adipose tissue and intracapsular brown adipose tissue is decreased by 69% (9 nmol/g/min vs 28 nmol/g/min) and 84% (37 nmol/g/min vs 237 nmol/g/min), respectively

increased adipocyte glucose uptake ( J:110773 )

• in 10 week old mutants insulin-stimulated uptake is increased 2-fold in white adipose tissue (26 vs 13 nmol/g/min) and brown adipose tissue (453 vs 224 nmol/g/min) compared to young controls

• in young mutants treated from 12 weeks of age with phloridzin, insulin-stimulated uptake in brown adipose tissue is increased (633 vs 247 nmol/g/min) but is unchanged in white adipose tissue

digestive/alimentary system

decreased intestinal glucose absorption ( J:110773 )

• in 21-week old mutants during a 2 hour hyperinsulinemic-euglycemic clamp insulin stimulated whole body uptake is decreased by 55% in muscle-specific knockout mice (102 umol/kg/min vs 224 umol/kg/min)

• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated whole body uptake in 10-week old mutants is decreased by 49% (130 vs 256 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, whole body uptake is decreased by 32% (142 vs 224 umol/kg/min)

cellular

decreased adipocyte glucose uptake ( J:110773 )

• insulin-stimulated glucose uptake in white adipose tissue and intracapsular brown adipose tissue is decreased by 69% (9 nmol/g/min vs 28 nmol/g/min) and 84% (37 nmol/g/min vs 237 nmol/g/min), respectively

increased adipocyte glucose uptake ( J:110773 )

• in 10 week old mutants insulin-stimulated uptake is increased 2-fold in white adipose tissue (26 vs 13 nmol/g/min) and brown adipose tissue (453 vs 224 nmol/g/min) compared to young controls

• in young mutants treated from 12 weeks of age with phloridzin, insulin-stimulated uptake in brown adipose tissue is increased (633 vs 247 nmol/g/min) but is unchanged in white adipose tissue

decreased muscle cell glucose uptake ( J:110773 )

• uptake in skeletal (gastrocnemius) muscle is decreased by 92% in muscle-specific knockouts (20 vs 237 nmol/g/min in controls)

• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated uptake in skeletal muscle in 10-week old mutants is decreased by 85% (39 vs 261 nmol/g/min in young controls)

• in young mutants treated from 12 weeks of age with phloridzin, skeletal muscle uptake is decreased by 81% (49 vs 227 nmol/g/min)

Genotype
MGI:3663418

cn48

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4⁺; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJae * FVB

digestive/alimentary system

decreased intestinal glucose absorption ( J:110773 )

• insulin stimulated whole body uptake is decreased in heterozygous muscle-specific knockout mice

muscle

decreased muscle cell glucose uptake ( J:110773 )

• insulin stimulated muscle uptake is decreased in heterozygous muscle-specific knockout mice

cellular

decreased muscle cell glucose uptake ( J:110773 )

• insulin stimulated muscle uptake is decreased in heterozygous muscle-specific knockout mice

Genotype
MGI:4944271

cn49

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129S4/SvJae * FVB

muscle

enhanced skeletal muscle regeneration ( J:169364 )

• in mice fed a normal diet, the weights of injured tibialis anterior muscles are greater than weights of muscles in controls

• regenerating myofibers after injury are larger compared to control injured myofibers, indicating that mutants exhibit a promotion in regeneration of injured muscles

• after 8 months of a high-fat diet, mutants exhibit larger myofiber sizes of regenerating muscles at 6 and 12 days after injury and increased weights of the injured tibialis anterior muscles than controls

• after 8 months on a high-fat diet, collagen deposition is reduced in regenerating muscles compared to controls

homeostasis/metabolism

decreased circulating glucose level ( J:169364 )

• after 8 months of a high-fat diet, mutants exhibit lower glucose levels than controls on the same diet

decreased circulating insulin level ( J:169364 )

• after 8 months of a high-fat diet, mutants exhibit lower insulin levels than controls on the same diet

Genotype
MGI:5829560

cn50

• Allelic Composition: Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJaeSor * FVB

Aberrant cardiomyocyte oranization and contractility in Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Ckmm-cre)5Khn/0 hearts

mortality/aging

postnatal lethality, complete penetrance ( J:223139 )

• although born at normal Mendelian ratios, all mice die abruptly from heart failure around 14 days after birth

cardiovascular system

abnormal myocardial fiber morphology ( J:223139 )

• cardiomyocytes appear disorganized, slightly hypertrophic, and are surrounded by more white space upon H&E staining

• trichrome staining revealed an increased blue signal between cardiomyocytes, suggesting increased expression of the extracellular matrix

• cardiomyocytes show abnormal actin dynamics and shortened sarcomeres

decreased myocardial fiber number ( J:223139 )

• overall density of cardiomyocytes is reduced, likely due to heart remodeling

increased myocardial fiber size ( J:223139 )

• cardiomyocytes appear slightly hypertrophic

• however, no major cardiac hypertrophy is observed at P12

thin interventricular septum ( J:223139 )

• thinning of the ventricle septum is noted at P14

thin ventricular wall ( J:223139 )

• thinning of the ventricle wall is noted at P14

dilated heart ventricle ( J:223139 )

• mice show progressive dilation of the heart ventricle chambers

dilated heart left ventricle ( J:223139 )

• dilation of the left ventricle chamber is observed as early as P7

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy

decreased ventricle muscle contractility ( J:223139 )

• fractional shortening (FS) is significantly reduced (below 20%) relative to controls (above 60%)

• reduced FS is detected as early as P6, and this decrease progresses rapidly to the time of death

decreased cardiac muscle relaxation ( J:223139 )

• ability of sarcomeres to fully relax is impaired in cardiomyocytes

abnormal heart echocardiography feature ( J:223139 )

• at P11, B- and M-mode images of echocardiography show a dramatic increase of left ventricular anterior-to-posterior wall diameter during systole and diastole

abnormal myocardial fiber physiology ( J:223139 )

• cardiomyocytes show abnormal actin dynamics and contractility defects

increased cardiomyocyte apoptosis ( J:223139 )

• at P13, hearts exhibit a slightly higher level of apoptosis than control hearts, as determined by cleaved caspase 3 staining

congestive heart failure ( J:223139 )

• cardiac malfunction starts early after birth and progresses rapidly to cardiac failure

• however, no differences in heart rate are observed from P3 to P11

muscle

abnormal myocardial fiber morphology ( J:223139 )

• cardiomyocytes appear disorganized, slightly hypertrophic, and are surrounded by more white space upon H&E staining

• trichrome staining revealed an increased blue signal between cardiomyocytes, suggesting increased expression of the extracellular matrix

• cardiomyocytes show abnormal actin dynamics and shortened sarcomeres

decreased myocardial fiber number ( J:223139 )

• overall density of cardiomyocytes is reduced, likely due to heart remodeling

increased myocardial fiber size ( J:223139 )

• cardiomyocytes appear slightly hypertrophic

• however, no major cardiac hypertrophy is observed at P12

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy

decreased ventricle muscle contractility ( J:223139 )

• fractional shortening (FS) is significantly reduced (below 20%) relative to controls (above 60%)

• reduced FS is detected as early as P6, and this decrease progresses rapidly to the time of death

decreased cardiac muscle relaxation ( J:223139 )

• ability of sarcomeres to fully relax is impaired in cardiomyocytes

increased cardiomyocyte apoptosis ( J:223139 )

• at P13, hearts exhibit a slightly higher level of apoptosis than control hearts, as determined by cleaved caspase 3 staining

abnormal sarcomere morphology ( J:223139 )

• under conditions of muscle relaxation, the lengths of sarcomeres and I bands are markedly reduced in cardiomyocytes

• at P11, the average length of sarcomeres (Z line to Z line) is only 1.68 um versus ~2.24 um in controls

• some regions of sarcomeres lack mitochondria coverage

abnormal I band morphology ( J:223139 )

• the lengths of I bands are markedly reduced in cardiomyocytes

cellular

increased cardiomyocyte apoptosis ( J:223139 )

• at P13, hearts exhibit a slightly higher level of apoptosis than control hearts, as determined by cleaved caspase 3 staining

decreased mitochondrial number ( J:223139 )

• some regions of sarcomeres lack mitochondria coverage

Genotype
MGI:5829563

cn51

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-GCaMP5)Ryba}/Gt(ROSA)26Sor⁺; Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJaeSor * FVB

cardiovascular system

decreased cardiac muscle contractility ( J:223139 )

• amplitude of heart contraction is significantly reduced relative to that in control hearts

• analysis of calcium cycling and heart contraction revealed impaired calcium handling

• hearts reach the maximal calcium level slightly slower than control hearts

• rate of post-contraction calcium decrease is significantly slower than that in controls hearts

• calcium decays almost linearly from the peak signal, in contrast to a two-phase (a rapid drop within the first 20 ms followed by a slower decrease for about 200 ms) reduction in control hearts

muscle

decreased cardiac muscle contractility ( J:223139 )

• amplitude of heart contraction is significantly reduced relative to that in control hearts

• analysis of calcium cycling and heart contraction revealed impaired calcium handling

• hearts reach the maximal calcium level slightly slower than control hearts

• rate of post-contraction calcium decrease is significantly slower than that in controls hearts

• calcium decays almost linearly from the peak signal, in contrast to a two-phase (a rapid drop within the first 20 ms followed by a slower decrease for about 200 ms) reduction in control hearts

Genotype
MGI:3609012

cn52

• Allelic Composition: Pik3r1^tm1Lca/Pik3r1^tm1Lca; Pik3r2^tm1Lca/Pik3r2^tm1Lca; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB

cardiovascular system

decreased myocardial fiber size ( J:102176 )

• most cardiomyocytes are reduced in size

decreased heart weight ( J:102176 )

• heart size normalized to body weight or tibia length is about 20% smaller than in wild-type mice; however the structure of the heart is normal with no obvious signs of fibrosis or tissue damage

• the increase in heart size in response to exercise is decreased compared to wild-type mice

muscle

decreased myocardial fiber size ( J:102176 )

• most cardiomyocytes are reduced in size

Genotype
MGI:5792903

cn53

• Allelic Composition: Hjv^tm1Kpan/Hjv^tm1Kpan; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB

normal phenotype

no abnormal phenotype detected ( J:231428 )

♂ • mice appear overtly normal, exhibit normal serum iron indices and do not develop iron overload in the liver, pancreas or heart, suggesting normal systemic iron homeostasis under physiological conditions

Genotype
MGI:3609011

cn54

• Allelic Composition: Pik3r1^tm1Lca/Pik3r1^tm1Lca; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB

normal phenotype

no abnormal phenotype detected ( J:102176 )

• mutants are viable and fertile, with no gross abnormalities and normal muscle morphology

Genotype
MGI:5883288

cn55

• Allelic Composition: Neb^tm2Hgra/Neb^tm2Hgra; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S6/SvEvTac * FVB

mortality/aging

premature death ( J:225840 )

• about half of mice die within 3 months of birth, with a median survival of 83 days

• most of the remaining mice survive into adulthood

muscle

decreased quadriceps weight ( J:225840 )

• quadriceps muscle weights are 60-70% smaller than in controls

abnormal muscle fiber morphology ( J:225840 )

• local areas with nemaline rods are seen; in both soleus and EDL muscle, rod bodies make up about 3% of the fiber area

abnormal sarcomere morphology ( J:225840 )

• H-zones are absent and A-band density gradually decreases toward the M-band, indicating thin filaments of variable length

• soleus and EDL muscle show a reduction in thin filament length

abnormal A band morphology ( J:225840 )

• A-band density gradually decreases toward the M-band

abnormal H zone morphology ( J:225840 )

• H-zones are absent

abnormal Z line morphology ( J:225840 )

• Z-disks of sarcomeres are often irregular and wavy

abnormal skeletal muscle fiber size ( J:225840 )

• in the soleus muscle, all three fiber types are smaller

• in the EDL, type IIB fibers are smaller

• the quadriceps muscle shows a severe reduction in type IIB fiber size

• in the EDL muscle, type I and IIA fibers are larger

increased skeletal muscle fiber number ( J:225840 )

• in the soleus muscle, the total number of fibers is increased

decreased skeletal muscle weight ( J:225840 )

• gastrocnemius muscle weights are 60-70% smaller than in controls

• tibialis cranialis and extensor digitorum longus (EDL) weights are much smaller at 5 weeks but less at 6 months

• the soleus muscle weight is increased by about 50% at 6 months

abnormal skeletal muscle fiber type ratio ( J:225840 )

• muscles show a consistent fiber-type switch away from type IIB fibers to oxidative types with hypertrophy of type I and IIA fiber types and severe atrophy of remaining type IIB fibers

• soleus muscle is nearly all type I fibers

• the EDL muscle shows an increased proportion of type I and IIA fibers and a much reduced number of type IIB

• the quadriceps muscle shows a severe reduction in type IIB fiber number

impaired skeletal muscle contractility ( J:225840 )

• reduced force-generating capacity of skeletal muscle, with tetanic force levels reduced 80-90% in EDL muscle

• the maximal specific force at optimal sarcomere length is reduced in both soleus and EDL muscle

behavior/neurological

impaired exercise endurance ( J:225840 )

• mice exercise with reduced duration, speed and distance ran

growth/size/body

decreased body weight ( J:225840 )

• about 40% lower body weight

homeostasis/metabolism

impaired exercise endurance ( J:225840 )

• mice exercise with reduced duration, speed and distance ran

limbs/digits/tail

decreased quadriceps weight ( J:225840 )

• quadriceps muscle weights are 60-70% smaller than in controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nemaline myopathy 2		DOID:0110928	OMIM:256030	J:225840

Genotype
MGI:4359072

cn56

• Allelic Composition: Aplp2^tm1Dbo/Aplp2^tm1Dbo; App^tm1.1Zhe/App^tm1.1Zhe; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * FVB

nervous system

abnormal neuromuscular synapse morphology ( J:152457 )

• at E16.5, endplate band width and number are increased compared to in wild-type mice that is as severe as in Aplp2^tm1Dbo App^tm1.2Zhe double homozygotes

• at P0, presynaptic and postsynaptic terminal distribution is diffuse and nerve terminal sprouting occurs unlike in wild-type that is as severe as in Aplp2^tm1Dbo App^tm1.2Zhe double homozygotesmice

abnormal miniature endplate potential ( J:152457 )

• reduced frequency

Genotype
MGI:5293356

cn57

• Allelic Composition: Fkbp1a^tm1Slh/Fkbp1a^tm1Slh; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB

muscle

abnormal skeletal muscle morphology ( J:176731 )

• muscles exhibit increased abnormal mitochondrial compared with wild-type muscles

abnormal muscle physiology ( J:176731 )

• extensor digitorum longus muscle-specific force and action potential-triggered calcium transient amplitudes are reduced compared to in wild-type muscles

• muscles exhibit leaky calcium channels indicated by enhanced frequency of calcium sparks compared with wild-type mice

• muscles exhibit S107-resistant oxidative stress unlike wild-type muscles

• S107-treatment does not improve abnormal muscle physiology

abnormal muscle contractility ( J:176731 )

• extensor digitorum longus muscle-specific force is reduced compared to in wild-type muscles

homeostasis/metabolism

impaired exercise endurance ( J:176731 )

• reduced

cellular

oxidative stress ( J:176731 )

• S107-resistant oxidative stress in muscles

behavior/neurological

impaired exercise endurance ( J:176731 )

• reduced

Genotype
MGI:5490256

cn58

• Allelic Composition: Fkbp1a^tm1.1Shou/Fkbp1a^tm1Zuk; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB

cardiovascular system

cardiovascular system phenotype ( J:195489 )

N • cardiac development appears normal

Genotype
MGI:3521579

cn59

• Allelic Composition: Fkbp1a^tm1Zuk/Fkbp1a^tm1Slh; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB

growth/size/body

decreased body weight ( J:94747 )

• males at 3 months of age started to weigh less (26.3 g) than wild-type (31.9 g), while females had similar weights

muscle

abnormal skeletal muscle fiber morphology ( J:94747 )

• mRNAs for all three isoforms of calcineurin A are significantly elevated in the diaphragm muscle; a significant increase in calcineurin protein levels is seen in diaphragm muscle homogenates from the mutant mice.

• no difference observed in calcineurin protein level in EDL and soleus muscles between mutant mice and controls

centrally nucleated skeletal muscle fibers ( J:94747 )

• the diaphragm exhibits an increased percentage of muscle fibers containing internal nuclei

abnormal skeletal muscle fiber type ratio ( J:94747 )

• the diaphragm muscle shows a shift in fast to slow muscle fiber ratio (i.e. of type I to type II fibers)

abnormal muscle physiology ( J:94747 )

• mutant myotubes exhibit a reduced maximal voltage-gated Ca2+ release, but decay of the Ca2+transients is not significantly different in the mutant and control

• mutant myotubes were more sensitive to caffeine-induced Ca2+ release than controls

• no significant differences in resting Ca2+ levels

abnormal muscle contractility ( J:94747 )

• greater tetanic force in the diaphragm than in controls at frequencies between 15 and 50 Hz; however, isometric tetanic force in the extensor digitorum longus (EDL) muscles was 19-32% less than controls at stimulation frequencies between 60 and 300 Hz

• abnormal calcium homeostasis

homeostasis/metabolism

abnormal calcium ion homeostasis ( J:94747 )

• mutant myotubes exhibit a reduced maximal voltage-gated Ca2+ release, but decay of the Ca2+transients is not significantly different in the mutant and control

• mutant myotubes were more sensitive to caffeine-induced Ca2+ release than controls

• no significant differences in resting Ca2+ levels

Genotype
MGI:5294403

cn60

• Allelic Composition: Pnpla2^tm1Eek/Pnpla2^tm1Eek; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S * FVB/N

cardiovascular system

increased cardiac muscle triglyceride level ( J:176252 )

• 10.7-fold in cardiac muscle

increased heart weight ( J:176252 )

• 1.5-fold

growth/size/body

increased heart weight ( J:176252 )

• 1.5-fold

homeostasis/metabolism

increased cardiac muscle triglyceride level ( J:176252 )

• 10.7-fold in cardiac muscle

muscle

increased cardiac muscle triglyceride level ( J:176252 )

• 10.7-fold in cardiac muscle

Genotype
MGI:5435675

cn61

• Allelic Composition: Fktn^tm1Kcam/Fktn^tm1Kcam; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129S/SvEv * FVB

muscle

dystrophic muscle ( J:187144 )

• signs of dystrophic disease at 12 weeks of age

• central nucleation in muscle fibers

• variable fiber size

• hypercontracted fibers

homeostasis/metabolism

increased circulating creatine kinase level ( J:187144 )

• elevated serum creatine kinase at 12 weeks of age

behavior/neurological

weakness ( J:187144 )

• reduced running times on a treadmill

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fukuyama congenital muscular dystrophy		DOID:0050559	OMIM:253800	J:187144

Genotype
MGI:3775313

cn62

• Allelic Composition: Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz; Insr^tm1Khn/Insr⁺; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB

cardiovascular system

cardiovascular system phenotype ( J:118987 )

N • heart function and morphology is normal

growth/size/body

growth/size/body region phenotype ( J:118987 )

N • mice exhibit normal growth rates

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N • mice exhibit normal glucose homeostasis

Genotype
MGI:3775310

cn63

• Allelic Composition: Igf1r^tm1.1Mhz/Igf1r⁺; Insr^tm1Khn/Insr^tm1Khn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB

mortality/aging

premature death ( J:118987 )

• 3 of 13 mice die by 6 months of age

cardiovascular system

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 23% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

respiratory system

abnormal breathing pattern ( J:118987 )

• beginning at 3 months of age, 1 of 13 mice appear to gasp for air

behavior/neurological

decreased locomotor activity ( J:118987 )

• beginning at 3 months of age, 1 of 13 mice exhibit less activity than wild-type mice

muscle

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 23% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N • mice exhibit normal glucose homeostasis

Genotype
MGI:3775311

cn64

• Allelic Composition: Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz; Insr^tm1Khn/Insr^tm1Khn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB

mortality/aging

postnatal lethality, complete penetrance ( J:118987 )

• mice die within the first month usually after birth 2 days after beginning to gasp for air at P16

• death is either spontaneous or precipitated by the stress of routine handling

cardiovascular system

abnormal myocardial fiber morphology ( J:118987 )

• mice exhibit irregular and disrupted sarcomeric Z and M lines and increased mitochondria with central crowding compared to wild-type hearts

decreased myocardial fiber size ( J:118987 )

thin interventricular septum ( J:118987 )

• thin at P17

small heart ( J:118987 )

decreased heart weight ( J:118987 )

• at P8 and P20, heart weights reduced 15% and 25%, respectively, compared to in wild-type mice

• mice exhibit decreased heart weight to body weight

abnormal heart left ventricle morphology ( J:118987 )

• at P17, mice exhibit an increase in left ventricle diameter of 6.7% in diastolic and 57.1% in systolic states

thin ventricular wall ( J:118987 )

• at P17

cardiac interstitial fibrosis ( J:118987 )

dilated cardiomyopathy ( J:118987 )

• at P17

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 33% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

decreased heart rate ( J:118987 )

congestive heart failure ( J:118987 )

behavior/neurological

decreased locomotor activity ( J:118987 )

• at P16, mice become less active than wild-type mice

respiratory system

abnormal breathing pattern ( J:118987 )

• at P16, mice gasp for air

growth/size/body

decreased body weight ( J:118987 )

• at P20, mice weigh 15% to 20% less than wild-type mice

postnatal growth retardation ( J:118987 )

• despite normal growth rates during the first two weeks after birth, mice exhibit reduced growth rates during week 3

muscle

abnormal myocardial fiber morphology ( J:118987 )

• mice exhibit irregular and disrupted sarcomeric Z and M lines and increased mitochondria with central crowding compared to wild-type hearts

decreased myocardial fiber size ( J:118987 )

dilated cardiomyopathy ( J:118987 )

• at P17

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 33% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N • mice exhibit normal glucose homeostasis

cellular

cardiac interstitial fibrosis ( J:118987 )

Genotype
MGI:3029365

cn65

• Allelic Composition: Slc2a4^tm1Abel/Slc2a4^tm1Abel; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129/Sv * C57BL/6

growth/size/body

decreased body weight ( J:75418 )

• growth was normal up to about 6 months

• weight gain became slower in older animals

• heart weight to body weight ratio increased 55% by 10 weeks of age

homeostasis/metabolism

abnormal circulating glucose level ( J:75418 )

• fasting and fed blood glucose levels increased from 2 to 4 months and then plateaued

hyperglycemia ( J:75418 )

• at 4 months both fed and fasted mice were hyperglycemic

abnormal glucose tolerance ( J:75418 )

• impaired glucose tolerance by 2 months and progressed until 4 months

increased liver glycogen level ( J:75418 )

• liver glycogen levels up 450%, comparable to increase in glucose uptake by liver

insulin resistance ( J:75418 )

• as early as 8 weeks in muscle

• glucose levels did not decrease in males in response to insulin injection and decreased by 34% in females

abnormal lipid homeostasis ( J:75418 )

abnormal lipid level ( J:75418 )

• cholesterol and free faty acid levels normal to 6 months of age

decreased fatty acids level ( J:75418 )

• fasting beta-hydroxybuterate levels lowered

decreased triglyceride level ( J:75418 )

muscle

muscle phenotype ( J:75418 )

N • muscle mass was normal

abnormal muscle physiology ( J:75418 )

• lactate levels in muscles of male mice were reduced

decreased muscle cell glucose uptake ( J:75418 )

• basal glucose uptake reduced 73-88% in skeletal muscle

• insulin and contraction both fail to stimulate glucose transport

liver/biliary system

increased liver glycogen level ( J:75418 )

• liver glycogen levels up 450%, comparable to increase in glucose uptake by liver

cellular

decreased muscle cell glucose uptake ( J:75418 )

• basal glucose uptake reduced 73-88% in skeletal muscle

• insulin and contraction both fail to stimulate glucose transport

Genotype
MGI:3697622

cn66

• Allelic Composition: Ptpn11^tm1Yan/Ptpn11^tm1Yan; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB

muscle

decreased skeletal muscle fiber size ( J:114499 )

• exhibit a decrease in skeletal myofiber size concomitant with a reduction in larger myofibers as well as a decrease in myonuclear number

decreased skeletal muscle fiber number ( J:114499 )

• exhibit a decrease in the number of skeletal muscle fibers, more specifically a reduction in type I slow muscle fibers

Genotype
MGI:3775312

cn67

• Allelic Composition: Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB

cardiovascular system

increased heart weight ( J:118987 )

• mice exhibit increased heart weight

• however, heart function is normal

growth/size/body

growth/size/body region phenotype ( J:118987 )

N • mice exhibit normal growth rates

increased heart weight ( J:118987 )

• mice exhibit increased heart weight

• however, heart function is normal

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N • mice exhibit normal glucose homeostasis

Genotype
MGI:2677593

cn68

• Allelic Composition: Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: BALB/c

mortality/aging

premature death ( J:85498 )

• normal numbers born

• normal phenotype and survive to wk 5

• growth normal

• breathe and eat normally

• normal activity

• not diabetic to wk 8

• all die at age 5-11 wks

• drop in activity 2-3 days before death and weight loss

• noncardiac muscle normal

cardiovascular system

abnormal cardiovascular system morphology ( J:85498 )

abnormal heart morphology ( J:85498 )

• by 6 wks, collagen levels, ANF and beta-myosin heavy chain levels are increased in hearts

• increased sensitivity of cardiomyocytes to hypoxia

abnormal myocardial fiber morphology ( J:85498 )

• cardiomyocytes appear more separated from each other

• reduction in cardiomyocyte volume

increased heart atrium size ( J:85498 )

• atria enlarge by 6 wks and massively inflated at death

small heart ( J:85498 )

• from 2-4 weeks, hearts became progressively smaller in relative terms but otherwise were normal

• by 6 weeks hearts were much smaller with reduced muscle mass due to smaller cardiomyocytes

myocardium hypoplasia ( J:85498 )

• muscle mass of hearts is significantly reduced

abnormal heart ventricle morphology ( J:85498 )

abnormal heart right ventricle morphology ( J:85498 )

• right ventricle is significantly enlarged by 6 weeks of age

heart right ventricle hypertrophy ( J:85498 )

• by 6 weeks

thin ventricular wall ( J:85498 )

• by 6 weeks

• extremely thin by death

dilated cardiomyopathy ( J:85498 )

• by 8 weeks of age, exhibit an increase in Z-line thickness, a feature of dilated cardiomyopathy

abnormal cardiovascular system physiology ( J:85498 )

• echocardiograms at 5-6 weeks revealing development of heart failure

decreased cardiac muscle contractility ( J:85498 )

• reduced fractional shortening and ejection fraction

growth/size/body

heart right ventricle hypertrophy ( J:85498 )

• by 6 weeks

decreased body weight ( J:85498 )

• observe a significant reduction in body weight 2-3 days before mutants die

muscle

abnormal myocardial fiber morphology ( J:85498 )

• cardiomyocytes appear more separated from each other

• reduction in cardiomyocyte volume

myocardium hypoplasia ( J:85498 )

• muscle mass of hearts is significantly reduced

heart right ventricle hypertrophy ( J:85498 )

• by 6 weeks

dilated cardiomyopathy ( J:85498 )

• by 8 weeks of age, exhibit an increase in Z-line thickness, a feature of dilated cardiomyopathy

decreased cardiac muscle contractility ( J:85498 )

• reduced fractional shortening and ejection fraction

abnormal Z line morphology ( J:85498 )

• thicker Z-line by 8 weeks of age

Genotype
MGI:6693480

cn69

• Allelic Composition: Bud23^em2Asil/Bud23^em2Asil; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

mortality/aging

premature death ( J:290738 )

• mice exhibit sudden death between 28 and 35 days of age

cellular

abnormal mitochondrial morphology ( J:290738 )

• although individual mitochondria are formed with a normal number of cristae, inter-myofibrillar mitochondria are markedly disorganized in cardiac tissue

• numerous spherical electron dense inclusion bodies are observed within the mitochondria of cardiac cells

decreased myocardial fiber mitochondrial DNA content ( J:290738 )

• mitochondrial DNA copy number is reduced in cardiac tissue

decreased mitochondrial number ( J:290738 )

• citrate synthase activity is significantly reduced in cardiac homogenates, indicating a reduction in cardiac mitochondrial density

abnormal oxidative phosphorylation ( J:290738 )

• mitochondrial oxidative phosphorylation (OXPHOS) is significantly reduced in cardiac homogenates

• however, LEAK respiration is normal

abnormal mitochondrial ATP synthesis coupled electron transport ( J:290738 )

• mitochondrial electron transfer capacity (ETC) is significantly reduced in cardiac homogenates

• reduction in OXPHOS results in a lower respiratory control ratio (RCR) indicating that mitochondria are less efficient at producing ATP; effects are apparent regardless of which substrate is used for electron donation

oxidative stress ( J:290738 )

• cardiomyocytes show a burden of increased reactive oxygen species resulting from the action of deranged mitochondria

• induction of NRF, suggesting adaptation to conditions of oxidative stress

cardiovascular system

decreased myocardial fiber mitochondrial DNA content ( J:290738 )

• mitochondrial DNA copy number is reduced in cardiac tissue

enlarged heart ( J:290738 )

• mice exhibit significant heart enlargement at P26

increased heart weight ( J:290738 )

• mice exhibit a significant heart weight to body weight ratio at P26

thin ventricular wall ( J:290738 )

• mice exhibit decreased left and right ventricle wall thickness at P26

dilated heart ventricle ( J:290738 )

• mice exhibit significantly dilated heart ventricles at P26

dilated heart left ventricle ( J:290738 )

• heart left ventricle is significantly dilated at P26-P28, indicating systolic dysfunction

cardiac fibrosis ( J:290738 )

• proteomics data revealed an upregulation of fibrosis markers in cardiac tissue

dilated cardiomyopathy ( J:290738 )

• mice develop severe dilated cardiomyopathy with early stages of heart failure observed around 26-28 days of age

• however, no pulmonary or liver edema is observed

decreased cardiac muscle contractility ( J:290738 )

• fractional shortening and relative wall thickness are significantly decreased at P26-P28

shortened QRS complex duration ( J:290738 )

• QRS interval is significantly shortened at P26-P28

• however, heart rate is normal

shortened QT interval ( J:290738 )

• corrected QT (QTc) interval is significantly shortened at P26-P28

• however, the JT interval is normal

congestive heart failure ( J:290738 )

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:290738 )

• heart shows evidence for an attempted switch to glycolytic ATP generation, with induction of rate-limiting glycolytic enzyme genes

abnormal protein level ( J:290738 )

• cardiac tissue recovered from P26 mice shows a significant reduction in the 18S/28S RNA ratio as well as a decrease in total protein concentration per cell

• mitochondria exhibit the largest loss of protein content, with small reciprocal increases seen in other compartments

abnormal enzyme/coenzyme activity ( J:290738 )

• citrate synthase activity is significantly reduced in cardiac homogenates, indicating a reduction in cardiac mitochondrial density

growth/size/body

enlarged heart ( J:290738 )

• mice exhibit significant heart enlargement at P26

increased heart weight ( J:290738 )

• mice exhibit a significant heart weight to body weight ratio at P26

muscle

decreased myocardial fiber mitochondrial DNA content ( J:290738 )

• mitochondrial DNA copy number is reduced in cardiac tissue

dilated cardiomyopathy ( J:290738 )

• mice develop severe dilated cardiomyopathy with early stages of heart failure observed around 26-28 days of age

• however, no pulmonary or liver edema is observed

decreased cardiac muscle contractility ( J:290738 )

• fractional shortening and relative wall thickness are significantly decreased at P26-P28

Genotype
MGI:5805262

cn70

• Allelic Composition: Oma1^tm1Tlan/Oma1^tm1Tlan; Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:229455 )

N • mice exhibit normal glucose tolerance

Genotype
MGI:5805260

cn71

• Allelic Composition: Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB

homeostasis/metabolism

decreased circulating insulin level ( J:229455 )

• lowered fasting insulin levels in the serum

• however, mice exhibit normal fasting blood glucose, weight gains and body composition

impaired glucose tolerance ( J:229455 )

• glucose intolerance

cardiovascular system

cardiovascular system phenotype ( J:229455 )

N • mice show normal heart function and normal cardiac uptake of glucose smaller mitochondria in hearts

mortality/aging

mortality/aging ( J:229455 )

N • mice show a normal life span, with a median life span of 125 weeks

Genotype
MGI:5316089

cn72

• Allelic Composition: Cfl2^tm1Itl/Cfl2^tm1Itl; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * C57BL/6NTac * FVB/N

mortality/aging

premature death ( J:182571 )

• mice live for 16 to 33 days

postnatal lethality, incomplete penetrance ( J:182571 )

• mice live for 16 to 33 days

muscle

abnormal Z line morphology ( J:182571 )

• dissolving

abnormal skeletal muscle morphology ( J:182571 )

• accumulation of F-actin

skeletal muscle fiber degeneration ( J:182571 )

• at P21, mice exhibit ballooning degeneration interspersed with normal-looking myofibers and pale core-like areas consistent with myofibrillar disruption and absent mitochondria unlike in wild-type mice

growth/size/body

decreased body size ( J:182571 )

decreased body weight ( J:182571 )

• 2- to 4-fold between P8 and P31

Genotype
MGI:5907992

cn73

• Allelic Composition: Sod2^tm1Shs/Sod2^tm1Shs; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6CrSlc * FVB

mortality/aging

premature death ( J:117386 )

• some mice begin to die at 8 weeks of age, and all mice die by 22 weeks of age, with a median survival rate of 15.4 weeks

growth/size/body

enlarged heart ( J:117386 )

• all mice show cardiac enlargement at 16 weeks of age

increased heart weight ( J:117386 )

• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months

decreased body weight ( J:117386 )

• mice show a 25% reduction in body weight at 16 weeks of age, without muscle atrophy

postnatal growth retardation ( J:117386 )

• mice begin to exhibit growth retardation at 8 weeks of age

cardiovascular system

abnormal cardiac muscle tissue morphology ( J:117386 )

• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls

increased cardiac muscle glycogen level ( J:117386 )

• interstitial storage of excess glycogen in hearts at 15 weeks of age

abnormal myocardium layer morphology ( J:117386 )

• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei

myocardial fiber degeneration ( J:117386 )

• left ventricular wall shows myocardial degeneration

• however, apoptotic cell death is not seen in myocardium or skeletal muscle

cardiac muscle necrosis ( J:117386 )

• some of the fibrotic foci are due to necrotic changes of the myocardium

enlarged heart ( J:117386 )

• all mice show cardiac enlargement at 16 weeks of age

increased heart weight ( J:117386 )

• hearts are 2.1-fold heavier at 2 months and 2.7-fold heavier at 4 months

abnormal heart left ventricle morphology ( J:117386 )

• left ventricular wall shows small mitochondria associated with scattered abnormal vacuoles

dilated heart ventricle ( J:117386 )

• dilation of both left and right ventricles

dilated heart left ventricle ( J:117386 )

• the left ventricular end-diastolic and end-systolic diameters are increased indicating left ventricular dilation

cardiac interstitial fibrosis ( J:117386 )

• diffuse fibrotic scars surround myocardial cells

• the majority of the thin layer of interstitial fibrosis is organized through the dilation of ventricles

dilated cardiomyopathy ( J:117386 )

• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy

decreased cardiac muscle contractility ( J:117386 )

• cardiac contractility is depressed in 2 and 4 month old mice as assessed by fractional shortening and ejection fraction

• mice administered the antioxidant manganese 5, 10, 15, 20-tetrakis (4-benxoic acid) porphyrin (MnTBAP) exhibit improvement in cardiac function but no effect on heart weight

abnormal heart echocardiography feature ( J:117386 )

• the left ventricular end-diastolic and end-systolic diameters are increased at 2 and 4 months of age indicating left ventricular dilation

• however, diastolic intraventricular septum thickness, diastolic left ventricular posterior wall thickness, and systolic left ventricular posterior wall thickness are not increased

congestive heart failure ( J:117386 )

• mice develop progressive congestive heart failure

behavior/neurological

decreased food intake ( J:117386 )

• mice show a 51% reduction in food intake

decreased locomotor activity ( J:117386 )

• mice hardly run on a running wheel apparatus when it is placed in their cage

• mice administered MnTBAP show improvement in physical activity

fatigue ( J:117386 )

• mice develop signs of fatigue as early as 8 weeks of age when mice begin to die

cellular

cardiac muscle necrosis ( J:117386 )

• some of the fibrotic foci are due to necrotic changes of the myocardium

cardiac interstitial fibrosis ( J:117386 )

• diffuse fibrotic scars surround myocardial cells

• the majority of the thin layer of interstitial fibrosis is organized through the dilation of ventricles

abnormal mitochondrial crista morphology ( J:117386 )

• cristae of mitochondria in the heart left ventricular wall are rough, irregular, abnormally wound, and concentrated in the central zone of the matrix

• however, no abnormal crystals or droplets in mitochondria are seen

decreased mitochondrial size ( J:117386 )

• heart left ventricular wall shows small mitochondria

abnormal oxidative phosphorylation ( J:117386 )

• mice show suppressed oxidative phosphorylation in myocardium with heart mitochondria generating less ATP

abnormal mitochondrial ATP synthesis coupled electron transport ( J:117386 )

• activity of Complex II is hardly detected in cardiac muscle and no enzymatic activity of Complex II is seen in skeletal muscle

• NADH-cytochrome c reductase activity in the heart and skeletal muscle is inhibited and succinate-cytochrome c reductase activity is reduced even more

oxidative stress ( J:117386 )

• mice exhibit enhanced reactive oxygen species (superoxide) generation with increased lipid peroxidation in heart and skeletal muscle mitochondria

• higher levels of malondialdehyde are detected in heart mitochondria, indicating oxidative damage in mitochondria

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:117386 )

• interstitial storage of excess glycogen in hearts at 15 weeks of age

muscle

abnormal cardiac muscle tissue morphology ( J:117386 )

• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls

increased cardiac muscle glycogen level ( J:117386 )

• interstitial storage of excess glycogen in hearts at 15 weeks of age

abnormal myocardium layer morphology ( J:117386 )

• left ventricular wall shows myocardial degeneration, myocyte disarray, vacuolization, and bizarre myocardial cells with irregular myofilaments and pleomorphic nuclei

myocardial fiber degeneration ( J:117386 )

• left ventricular wall shows myocardial degeneration

• however, apoptotic cell death is not seen in myocardium or skeletal muscle

cardiac muscle necrosis ( J:117386 )

• some of the fibrotic foci are due to necrotic changes of the myocardium

dilated cardiomyopathy ( J:117386 )

• myocardium exhibits pathology indicative of typical idiopathic dilated cardiomyopathy

decreased cardiac muscle contractility ( J:117386 )

• cardiac contractility is depressed in 2 and 4 month old mice as assessed by fractional shortening and ejection fraction

• mice administered the antioxidant manganese 5, 10, 15, 20-tetrakis (4-benxoic acid) porphyrin (MnTBAP) exhibit improvement in cardiac function but no effect on heart weight

abnormal skeletal muscle morphology ( J:117386 )

• skeletal muscle of the tibialis anterior muscle shows similar but modest ultrastructural defects as in cardiac muscle

• ATP contents in heart and skeletal muscle are decreased to about 30% of those of controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:117386

Genotype
MGI:5494711

cn74

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-MAP2K7*/MAPK8,-EGFP)Ftw}/Gt(ROSA)26Sor⁺; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

growth/size/body

growth/size/body region phenotype ( J:195844 )

N • mice exhibit normal body composition

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:195844 )

N • mice exhibit normal energy homeostasis, insulin signaling and glucose homeostasis

Genotype
MGI:3809846

cn75

• Allelic Composition: Txnip^tm1Road/Txnip^tm1Road; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

mortality/aging

mortality/aging ( J:132756 )

N • mice exhibit normal viability

homeostasis/metabolism

hypoglycemia ( J:132756 )

increased circulating ketone body level ( J:132756 )

increased circulating triglyceride level ( J:132756 )

improved glucose tolerance ( J:132756 )

reproductive system

reproductive system phenotype ( J:132756 )

N • mice exhibit normal reproduction

growth/size/body

growth/size/body region phenotype ( J:132756 )

N • mice exhibit normal growth

Genotype
MGI:4946937

cn76

• Allelic Composition: Lig3^tm1.1Pmc/Lig3^tm1.1Pmc; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

mortality/aging

premature death ( J:170077 )

• mice die between 3.5 and 4.5 weeks of age

cardiovascular system

abnormal myocardial fiber morphology ( J:170077 )

• with abnormal mitochondria

dilated heart atrium ( J:170077 )

enlarged heart ( J:170077 )

thin ventricular wall ( J:170077 )

dilated heart ventricle ( J:170077 )

abnormal cardiovascular system physiology ( J:170077 )

• mice exhibit decreased diastolic and systolic movements of the left ventricle wall and interventricular septum compared with wild-type mice

decreased cardiac muscle contractility ( J:170077 )

• fractional shortening and ejection fraction are decreased compared to in wild-type mice

muscle

abnormal myocardial fiber morphology ( J:170077 )

• with abnormal mitochondria

decreased cardiac muscle contractility ( J:170077 )

• fractional shortening and ejection fraction are decreased compared to in wild-type mice

growth/size/body

enlarged heart ( J:170077 )

Genotype
MGI:5293380

cn77

• Allelic Composition: Prkab1^tm1Grst/Prkab1^tm1Grst; Prkab2^tm1Grst/Prkab2^tm1Grst; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

muscle

decreased muscle cell glucose uptake ( J:176578 )

• decreased glucose uptake during exercise

abnormal skeletal muscle morphology ( J:176578 )

• decrease in intermyofibrillar mitochondrial content

• mitochondria in both the intermyofibrillar and subsarcolemmal regions are larger

increased muscle fatigability ( J:176578 )

• isolated EDL muscles fatigue rapidly

behavior/neurological

decreased locomotor activity ( J:176578 )

• decrease in voluntary wheel activity

impaired exercise endurance ( J:176578 )

• exercise intolerant and have dramatic reductions in both maximal running speed and distance covered

homeostasis/metabolism

impaired exercise endurance ( J:176578 )

• exercise intolerant and have dramatic reductions in both maximal running speed and distance covered

increased circulating glucose level ( J:176578 )

• elevated serum glucose following exercise

abnormal enzyme/coenzyme activity ( J:176578 )

• decrease in citrate synthase and cytochrome c oxidase activities

cellular

decreased muscle cell glucose uptake ( J:176578 )

• decreased glucose uptake during exercise

Genotype
MGI:5293381

cn78

• Allelic Composition: Prkab2^tm1Grst/Prkab2^tm1Grst; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

homeostasis/metabolism

impaired exercise endurance ( J:176578 )

• about a 25% reduction in running capacity

behavior/neurological

impaired exercise endurance ( J:176578 )

• about a 25% reduction in running capacity

Genotype
MGI:5496891

cn79

• Allelic Composition: Twnk^tm1.1Lrsn/Twnk^tm1.1Lrsn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

mortality/aging

premature death ( J:194965 )

• mice die at 19 weeks

cardiovascular system

enlarged heart ( J:194965 )

• mice show signs of progressive heart enlargement from age of 8 weeks

cellular

abnormal mitochondrial morphology ( J:194965 )

• severe depletion of mitochondrial DNA (mtDNA) is observed in heart-specific mutants; this results in decrease of mtDNA-encoded transcripts and mtDNA-encoded proteins like Cox1 and Cox2

abnormal respiratory electron transport chain ( J:194965 )

• in heart tissue, levels respiratory complexes and superassemblies containing mtDNA-encoded subunits are decreased complared to an exclusively nucleus-encoded complex indicating that the mutation results in defective respiratory chain assembly in heart mitochondria

growth/size/body

enlarged heart ( J:194965 )

• mice show signs of progressive heart enlargement from age of 8 weeks

Genotype
MGI:5514355

cn80

• Allelic Composition: Fktn^tm3.1Ttd/Fktn^tm3.1Ttd; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

muscle

skeletal muscle necrosis ( J:198535 )

• at 16 weeks

abnormal skeletal muscle fiber morphology ( J:198535 )

• exercised mice exhibit increased membrane-impermeable Evans blue dye uptake compared with cells from control mice

centrally nucleated skeletal muscle fibers ( J:198535 )

• at 16 weeks, increasing with age

dystrophic muscle ( J:198535 )

• at 16 weeks with myonecrosis and central nucleation

homeostasis/metabolism

increased circulating creatine kinase level ( J:198535 )

• at 16 weeks

• after forced exercise

cellular

skeletal muscle necrosis ( J:198535 )

• at 16 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
muscular dystrophy-dystroglycanopathy type B1		DOID:0050588	OMIM:613155	J:198535

Genotype
MGI:5550389

cn81

• Allelic Composition: Atf4^tm1.1Cmad/Atf4^tm1.1Cmad; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

muscle

muscle phenotype ( J:206503 )

N • mice exhibit normal skeletal muscle development

decreased susceptibility to induced muscular atrophy ( J:206503 )

• following fasting or 3 days of immobilization

• however, muscular atrophy following 7 days of immobilization is normal

Genotype
MGI:5897113

cn82

• Allelic Composition: Fnip1^tm1.1Baba/Fnip1^tm1.1Baba; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

muscle

abnormal muscle morphology ( J:220672 )

• red colored

abnormal muscle physiology ( J:220672 )

• increased mitochondrial biogenesis in muscle

cardiovascular system

cardiac hypertrophy ( J:220672 )

cellular

abnormal mitochondrial physiology ( J:220672 )

• increased mitochondrial biogenesis in muscle

growth/size/body

cardiac hypertrophy ( J:220672 )

Genotype
MGI:6151160

cn83

• Allelic Composition: Cnot1^tm1Tya/Cnot1^tm1Tya; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB

mortality/aging

postnatal lethality, complete penetrance ( J:260012 )

• mice die P10

cardiovascular system

cardiac muscle necrosis ( J:260012 )

decreased cardiac muscle contractility ( J:260012 )

prolonged QT interval ( J:260012 )

muscle

cardiac muscle necrosis ( J:260012 )

decreased cardiac muscle contractility ( J:260012 )

cellular

cardiac muscle necrosis ( J:260012 )

Genotype
MGI:6294482

cn84

• Allelic Composition: Nsun4^tm1.2Arte/Nsun4^tm1.2Arte; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6 * FVB/N * SJL

cardiovascular system

increased heart weight ( J:211012 )

• heart-to-body weight ratio increases with age

cellular

abnormal mitochondrial morphology ( J:211012 )

• increased mitochondrial mass as indicated by increased mtDNA level in heart at age 20 weeks

abnormal mitochondrial physiology ( J:211012 )

• strong increase in mitochondrial de novo transcription and steady-state transcript levels in heart

• strong inhibition of translation and severely reduced levels of assembled ribosomes in heart

• severely reduced ribosome self-assembly in heart

abnormal oxidative phosphorylation ( J:211012 )

• drastically reduced steady-state levels of assembled OXPHOS complexes containing mtDNA-encoded polypeptides in heart mitochondria from age 20 weeks

• unchanged steady-state levels of assembled OXPHOS complexes containing mtDNA-encoded polypeptides in heart mitochondria at age 5 weeks

• steady-state levels of complex II

mortality/aging

premature death ( J:211012 )

• mice die before age 25 weeks

growth/size/body

increased heart weight ( J:211012 )

• heart-to-body weight ratio increases with age

Genotype
MGI:7610682

cn85

• Allelic Composition: Gpcpd1^{tm1c(EUCOMM)Hmgu}/Gpcpd1^{tm1c(EUCOMM)Hmgu}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB

muscle

muscle phenotype ( J:345630 )

♂N • normal muscle development, morphology, and size at 6 and 20 months of age

♂N • distribution of fiber type, myofiber size, muscle and mitochondrial ultrastructure, and muscle strength are similar to controls at 20 months of age

increased muscle cell glucose uptake ( J:345630 )

♂ • increased uptake in skeletal and cardiac muscle at 12 weeks of age

♂ • no change in glucose uptake in white fat, subcutaneous fat, brown fat, or liver

increased cardiac muscle cell glucose uptake ( J:345630 )

♂ • at 12 weeks of age

abnormal muscle glycogen level ( J:345630 )

♂ • decreased muscle glycogen levels at 20 months of age

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:345630 )

♂N • blood insulin levels are similar to controls

increased insulin secretion ( J:345630 )

♂ • increased insulin release at 12 weeks of age

hyperglycemia ( J:345630 )

♂ • fed and fasting hyperglycemia at 20 months of age but not at 12 weeks of age

impaired glucose tolerance ( J:345630 )

♂ • severe glucose intolerance at 12 weeks and 20 months of age

♂ • severe defect in glucose clearance after 10 weeks on a high-sugar diet or high fat diet that is worse than in diet matched controls

♂ • however, no difference in weight gain is seen in mice on a high sugar or high fat diet compared to diet matched controls

abnormal muscle glycogen level ( J:345630 )

♂ • decreased muscle glycogen levels at 20 months of age

increased glycerophosphocholine level ( J:345630 )

• in muscle, resulting in an increase in muscle osmolarity in 24 month old mice

endocrine/exocrine glands

increased insulin secretion ( J:345630 )

♂ • increased insulin release at 12 weeks of age

cardiovascular system

increased cardiac muscle cell glucose uptake ( J:345630 )

♂ • at 12 weeks of age

cellular

increased muscle cell glucose uptake ( J:345630 )

♂ • increased uptake in skeletal and cardiac muscle at 12 weeks of age

♂ • no change in glucose uptake in white fat, subcutaneous fat, brown fat, or liver

increased cardiac muscle cell glucose uptake ( J:345630 )

♂ • at 12 weeks of age

Genotype
MGI:5660650

cn86

• Allelic Composition: Hmox1^tm1.1Hes/Hmox1^tm1.1Hes; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/N

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:214639 )

N • mice fed a high-fat diet exhibit similar body weight accumulation and glucose and insulin tolerance as controls

Genotype
MGI:6277926

cn87

• Allelic Composition: Gfpt1^{tm1c(EUCOMM)Wtsi}/Gfpt1^{tm1c(EUCOMM)Wtsi}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * SJL/J
• Cell Lines: EPD0069_2_H11

behavior/neurological

decreased grip strength ( J:265013 )

• starting at 6 weeks of age, mice show a significant reduction in the latency to fall from a wire grid at various time points up to 6 months of age in the inverted screen test assay

• however, the deficit in motor performance is not progressive over the first 6 months

muscle

muscle phenotype ( J:265013 )

N • no pathological changes are observed in cardiac muscle

abnormal sarcolemma morphology ( J:265013 )

• EM revealed the presence of ectopic subsarcolemmal caveolae-like vesicular structures in intercostal muscle, indicating ER-Golgi-stress

abnormal sarcoplasmic reticulum morphology ( J:265013 )

• soleus and tibialis anterior (TA) muscles show significantly larger sarcoplasmic caveolin-3 positive punctae than control muscles

abnormal skeletal muscle fiber morphology ( J:265013 )

• skeletal muscles show occasional rounded myofibers, a small number of fibers with internal nuclei, necrotic fibers, and presence of atrophic and hypertrophic myofibers, some of which exhibit splitting

• tubular aggregates are detected in some myofibers in all muscles examined along with the replacement of myofibers with adipose tissue, esp. in diaphragm muscle

• no differences in the fiber type proportion are observed in the soleus or TA muscles

• no tubular aggregate fiber type specific predominance is observed in the soleus or TA muscles

skeletal muscle fiber necrosis ( J:265013 )

• necrotic skeletal myofibers are observed

decreased skeletal muscle fiber size ( J:265013 )

• the intercostal and soleus muscles exhibit a shift towards smaller fibers (29% and 26%, respectively) relative to control muscles

skeletal muscle fiber atrophy ( J:265013 )

• at 3 months of age, the diaphragm muscle shows muscle fiber atrophy along with a progressive replacement of muscle tissue by fibroadipose tissue

increased skeletal muscle fiber size ( J:265013 )

• skeletal muscle fiber hypertrophy is observed; the EDL muscle exhibits a shift towards larger fibers (18%) relative to control muscle

increased variability of skeletal muscle fiber size ( J:265013 )

• differences in fiber size are greatest in EDL muscle (61%), followed by the soleus (56%), intercostal (29%) and TA (26%) muscles

• however, median cross-sectional area (CSA) values for TA muscle fiber size remain normal

centrally nucleated skeletal muscle fibers ( J:265013 )

• a small number of skeletal myofibers have centrally located nuclei

impaired skeletal muscle contractility ( J:265013 )

• at 3 months of age, the maximal isometric tetanic force in diaphragm muscle at 150 Hz is reduced by 35.3% relative to that in control mice

abnormal muscle electrophysiology ( J:265013 )

• at 3 months of age, a progressive decline in force generated by the TA muscle is evident from 80 tetanic nerve stimulations of the common peroneal nerve (CPN) at 120 Hz (80, 42.9%; 90, 47.7%; 100, 64.7%), whereas a significant (26.1%) reduction of force in control mice is only seen after 100 stimulations compared with baseline

• a progressive reduction in force generated by the diaphragm muscle is noted between 50 and 100 tetanic nerve stimulations at 150 Hz

increased muscle fatigability ( J:265013 )

• at 3 months of age, mice show a progressive increase in TA muscle fatigability, expressed as the % decrease of baseline force, after 80 (20.8%), 90 (26.4%) and 100 (38.7%) tetanic nerve stimulations at 120 Hz relative to control mice

• a progressive increase in diaphragm muscle fatigability is noted between 50 and 100 tetanic nerve stimulations at 150 Hz

muscle weakness ( J:265013 )

• mice exhibit muscle weakness as early as 6 weeks of age

myopathy ( J:265013 )

• mice develop progressive myopathic changes in TA, intercostal, soleus, extensor digitorum longus (EDL) and diaphragm muscles

nervous system

abnormal myelin sheath morphology ( J:265013 )

• presynaptic alterations in intercostal muscle NMJs include irregular and occasionally convoluted presynaptic myelin sheaths

decreased myelin sheath thickness ( J:265013 )

• the diameter of myelin sheaths is significantly reduced in intercostal muscle

abnormal neuromuscular synapse morphology ( J:265013 )

• at 3 months of age, acetylcholine receptor (AChR) clusters in TA, intercostal, soleus and EDL muscles appear smaller and fragmented relative to those in control muscles

• reduction in AChR cluster area is greatest in the TA (45%), followed by the EDL (33%), soleus (28%) and intercostal (27%) muscles

• mean number of fragments/AChR cluster is greatest in the soleus, followed by the EDL, intercostal and TA muscles

• presynaptic changes include discontinuous and disorganized axonal projections, thinner irregular myelin sheaths and remodeling of motor nerve terminals; however, axons can project normally to endplates with no signs of overshooting, retractions or axonal sprouting

• NMJs in intercostal muscle exhibit fewer postsynaptic junctional folds, accumulation of tubular aggregates and subsarcolemmal vesicular structures, deposits of dense filamentous-like material, irregular and convoluted presynaptic myelin sheaths, and a reduction in the diameter of myelin sheaths

• AChR turnover rate in TA muscles is normal

growth/size/body

growth/size/body region phenotype ( J:265013 )

N • although mice are slightly smaller than control mice, no significant differences in body weight are observed over the first 6 months

cellular

skeletal muscle fiber necrosis ( J:265013 )

• necrotic skeletal myofibers are observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital myasthenic syndrome 12		DOID:0110660	OMIM:610542	J:265013

Genotype
MGI:5427431

cn88

• Allelic Composition: Crat^tm1.1Pbrc/Crat^tm1.1Pbrc; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * FVB

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:184778 )

• gain more weight and more fat mass when placed on a high fat diet

• on a low fat diet body weight and fat mass are similar to wild-type

decreased circulating free fatty acids level ( J:184778 )

• on a low fat diet

decreased circulating triglyceride level ( J:184778 )

• on a low fat diet

abnormal glucose homeostasis ( J:184778 )

increased circulating glucose level ( J:184778 )

• both at baseline and throughout an intraperitoneal glucose tolerance test

• exacerbated on a high fat diet

impaired glucose tolerance ( J:184778 )

• glucose intolerant

• exacerbated on a high fat diet

insulin resistance ( J:184778 )

cellular

abnormal cellular respiration ( J:184778 )

• when pyruvate is the only carbon source addition of carnitine fails to increase state 3 respiration

• rates of CO2 production are increased in isolated muscle mitochondria when exposed to moderate or high concentrations of palmitate

abnormal aerobic respiration ( J:184778 )

• increase in whole body carbohydrate oxidation in response to an insulin challenge or during the fasting-to-fed transition is diminished

abnormal tricarboxylic acid cycle ( J:184778 )

• in isolated skeletal muscle mitochondria there is a near-complete loss of acyltransferase activity using various short chain acyl-CoA substrates

muscle

abnormal muscle physiology ( J:184778 )

• marked accumulation of several medium and long chain acylcarnitines in skeletal muscle and to a lesser degree in the heart

• impaired efflux of pyruvate dehydrogenase-derived acetylcarnitine from skeletal muscle

cardiovascular system

abnormal myocardial fiber physiology ( J:184778 )

• several short, medium, and long chain acyl-CoA species are elevated in the heart

growth/size/body

increased susceptibility to diet-induced obesity ( J:184778 )

• gain more weight and more fat mass when placed on a high fat diet

• on a low fat diet body weight and fat mass are similar to wild-type

Genotype
MGI:7545578

cn89

• Allelic Composition: Myhas^tm1Bcgen/Myhas^tm1Bcgen; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * FVB

muscle

decreased extensor digitorum longus weight ( J:240240 )

decreased gastrocnemius weight ( J:240240 )

decreased tibialis anterior weight ( J:240240 )

decreased skeletal muscle fiber diameter ( J:240240 )

skeletal muscle atrophy ( J:240240 )

muscle weakness ( J:240240 )

• reduced force and specific tetanic force as well as muscle performance in forced treadmill running tests

limbs/digits/tail

decreased extensor digitorum longus weight ( J:240240 )

decreased gastrocnemius weight ( J:240240 )

decreased tibialis anterior weight ( J:240240 )

Genotype
MGI:5613395

cn90

• Allelic Composition: Bmal1^tm1.1Shbi/Bmal1^tm1.1Shbi; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * FVB

behavior/neurological

behavior/neurological phenotype ( J:177865 )

N • mice exhibit normal locomotor activity

muscle

muscle phenotype ( J:177865 )

N • mice fed a normal or high fat diet exhibit almost normal skeletal muscle triglyceride content

Genotype
MGI:3622117

cn91

• Allelic Composition: Musk^tm1Vwi/Musk^tm1Vwi; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * FVB

mortality/aging

premature death ( J:106867 )

• die before P30

muscle

muscle weakness ( J:106867 )

• at around 2 to 3 weeks of age, develop severe muscle weakness with impaired mobility and difficulty breathing, eating, and drinking

nervous system

abnormal phrenic nerve innervation pattern to diaphragm ( J:106867 )

• in older mice, phrenic nerve innervation is seen outside the central band of the diaphragm muscle

abnormal neuromuscular synapse morphology ( J:106867 )

• from P20 on, endplates in the diaphragm show decreased acetylcholine receptor densities and begin to disintegrate

• after P20 neuromuscular junction endplates are seen outside the central band where they are normally confined

behavior/neurological

decreased grip strength ( J:106867 )

• grip strength from P12 onwards does not increase, unlike in wild-type mice

growth/size/body

weight loss ( J:106867 )

• normal weight gain until about 3 to 4 weeks of age then weight gain stops and weight loss is seen

skeleton

kyphosis ( J:106867 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital myasthenic syndrome 9		DOID:0110670	OMIM:616325	J:106867

Genotype
MGI:3622118

cn92

• Allelic Composition: Musk^tm1Vwi/Musk^tm1.1Vwi; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6J * FVB

mortality/aging

premature death ( J:106867 )

• die before P30

muscle

muscle weakness ( J:106867 )

• at around 2 to 3 weeks of age, develop severe muscle weakness with impaired mobility and difficulty breathing, eating, and drinking

nervous system

abnormal phrenic nerve innervation pattern to diaphragm ( J:106867 )

• in older mice, phrenic nerve innervation is seen outside the central band of the diaphragm muscle

abnormal neuromuscular synapse morphology ( J:106867 )

• from P20 on, endplates in the diaphragm show decreased acetylcholine receptor densities and begin to disintegrate

• after P20 neuromuscular junction endplates are seen outside the central band where they are normally confined

behavior/neurological

decreased grip strength ( J:106867 )

• grip strength from P12 onwards does not increase, unlike in wild-type mice

growth/size/body

weight loss ( J:106867 )

• normal weight gain until about 3 to 4 weeks of age then weight gain stops and weight loss is seen

skeleton

kyphosis ( J:106867 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital myasthenic syndrome 9		DOID:0110670	OMIM:616325	J:106867

Genotype
MGI:6407437

cn93

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-LMNA*)Cyh}/Gt(ROSA)26Sor⁺; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6JNarl * FVB

mortality/aging

premature death ( J:284048 )

• median lifespan of 40 days

growth/size/body

decreased body fat mass ( J:284048 )

♂ • net volume and ratio of fat mass is lower

decreased body size ( J:284048 )

• adults (2 months of age) appear smaller, with decreased size beginning at 3 weeks after birth

• body weight of 2 month old males is about 35% lower than in controls

muscle

abnormal skeletal muscle morphology ( J:284048 )

• skeletal muscle shows dilated endoplasmic reticulum lumen, reduced mitochondrial cristae density, and ruffled nucleus morphology

decreased skeletal muscle fiber diameter ( J:284048 )

• reduction in muscle cross-sectional area of the soleus muscle

centrally nucleated skeletal muscle fibers ( J:284048 )

• increase in the prevalence of central nuclei in the myofibrils of the soleus muscle

decreased skeletal muscle mass ( J:284048 )

• reduction in muscle mass

dystrophic muscle ( J:284048 )

adipose tissue

decreased body fat mass ( J:284048 )

♂ • net volume and ratio of fat mass is lower

abnormal white adipose tissue morphology ( J:284048 )

♂ • cell volume of white adipose tissue is lower

♂ • however, histology of brown adipose tissue is unaffected and lean mass is unaffected

behavior/neurological

jerky movement ( J:284048 )

♂ • frequency of twitching is increased

decreased grip strength ( J:284048 )

♂ • 50% reduction in grip strength

decreased locomotor activity ( J:284048 )

♂ • mice show reductions in the frequencies of drinking, hanging, rearing and walking during the night indicating that mice are less active at night

♂ • however, no differences in daytime activity are seen

cardiovascular system

decreased heart rate ( J:284048 )

prolonged QT interval ( J:284048 )

cellular

abnormal cell nucleus morphology ( J:284048 )

• nuclear morphology of skeletal muscle becomes ruffled

abnormal endoplasmic reticulum morphology ( J:284048 )

• endoplasmic reticulum lumen in the myonuclei is dilated

abnormal mitochondrial crista morphology ( J:284048 )

• density of mitochondrial cristae is reduced is skeletal muscle

increased endoplasmic reticulum stress ( J:284048 )

• marker analysis indicates elevated ER stress in skeletal muscle

homeostasis/metabolism

increased circulating creatine kinase level ( J:284048 )

decreased body temperature ( J:284048 )

♂ • surface temperature of the eye and the trunk is lower indicating lower body temperature

decreased carbon dioxide production ( J:284048 )

♂ • carbon dioxide production per unit activity is lower during the night

decreased oxygen consumption ( J:284048 )

♂ • whole-body consumption of oxygen is lower during the night

increased respiratory quotient ( J:284048 )

♂ • the respiratory exchange ratio is increased during the day

decreased basal metabolism ( J:284048 )

♂ • heat production is lower at night but not during the day

skeleton

kyphosis ( J:284048 )

• adults present kyphosis

Genotype
MGI:7580966

cn94

• Allelic Composition: Mtif3^{tm1c(EUCOMM)Wtsi}/Mtif3^{tm1c(EUCOMM)Wtsi}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N

cardiovascular system

thin interventricular septum ( J:287609 )

• found at 25 weeks of age

increased heart weight ( J:287609 )

• increased heart weight/tibial length

decreased heart left ventricle posterior wall thickness ( J:287609 )

• thin left ventricular posterior wall (LVPW) found at 25 weeks of age

decreased cardiac muscle contractility ( J:287609 )

• decreased fractional shortening found at 25 weeks of agefound at 25 weeks of age

cardiomyopathy ( J:287609 )

• cellular disarray and necrotic foci found in cardiac tissue at 10 and 25 weeks of age

growth/size/body

increased heart weight ( J:287609 )

• increased heart weight/tibial length

decreased body weight ( J:287609 )

• mice are significantly lighter compared to control mice starting at 3 weeks of age to 25 weeks

muscle

decreased cardiac muscle contractility ( J:287609 )

• decreased fractional shortening found at 25 weeks of agefound at 25 weeks of age

cardiomyopathy ( J:287609 )

• cellular disarray and necrotic foci found in cardiac tissue at 10 and 25 weeks of age

decreased skeletal muscle fiber size ( J:287609 )

• decreased size of specific fibers in the skeletal muscle of 25-week-old knockout mice

centrally nucleated skeletal muscle fibers ( J:287609 )

• centralized nuclei in the skeletal muscle of 25-week-old knockout mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:287609

Genotype
MGI:5427445

cn95

• Allelic Composition: Pik3c3^{tm1c(EUCOMM)Wtsi}/Pik3c3^{tm1c(EUCOMM)Wtsi}; Tg(CAG-EGFP/Map1lc3b)53Nmz/0; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N * C57BL/6NCrj * FVB/N

cardiovascular system

abnormal myocardial fiber physiology ( J:182628 )

• hearts from fed and starved exhibit blocked autophagy flux compared with control hearts

cellular

abnormal autophagy ( J:182628 )

• hearts from fed and starved exhibit blocked autophagy flux compared with control hearts

homeostasis/metabolism

abnormal autophagy ( J:182628 )

• hearts from fed and starved exhibit blocked autophagy flux compared with control hearts

Genotype
MGI:6444642

cn96

• Allelic Composition: Fis1^tm1.1Itl/Fis1^tm1.1Itl; Tg(CAG-EGFP/Map1lc3b)53Nmz/0; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6NCrlj * C57BL/6NTac * DBA/2 * FVB

cellular

abnormal autophagy ( J:290485 )

• increased GFP-LC3 puncta containing mitochondria in the soleus of sedentary mice

homeostasis/metabolism

abnormal autophagy ( J:290485 )

• increased GFP-LC3 puncta containing mitochondria in the soleus of sedentary mice

Genotype
MGI:6151162

cn97

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; Cnot1^tm1Tya/Cnot1^tm1Tya; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj * FVB

mortality/aging

postnatal lethality, complete penetrance ( J:260012 )

• mice die by P15

cardiovascular system

cardiac muscle necrosis ( J:260012 )

• not as severe as in Cnot1^tm1Tya/Cnot1^tm1Tya Tg(Ckmm-cre)5Khn mice

decreased cardiac muscle contractility ( J:260012 )

• not as severe as in Cnot1^tm1Tya/Cnot1^tm1Tya Tg(Ckmm-cre)5Khn mice

muscle

cardiac muscle necrosis ( J:260012 )

• not as severe as in Cnot1^tm1Tya/Cnot1^tm1Tya Tg(Ckmm-cre)5Khn mice

decreased cardiac muscle contractility ( J:260012 )

• not as severe as in Cnot1^tm1Tya/Cnot1^tm1Tya Tg(Ckmm-cre)5Khn mice

cellular

cardiac muscle necrosis ( J:260012 )

• not as severe as in Cnot1^tm1Tya/Cnot1^tm1Tya Tg(Ckmm-cre)5Khn mice

Genotype
MGI:7433065

cn98

• Allelic Composition: Elac2^{tm1c(EUCOMM)Wtsi}/Elac2^{tm1c(EUCOMM)Wtsi}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N * FVB

mortality/aging

premature death ( J:265839 )

• mice exhibit a short life span and die by 4 weeks of age

• early-onset cardiomyopathy and death are due to the combined consequences of impaired tRNA processing in both mitochondria and the nucleus

growth/size/body

increased heart weight ( J:265839 )

• at 4 weeks of age, heart weight-to-body weight ratio is significantly higher than that in control mice

decreased body weight ( J:265839 )

• at 4 weeks of age, average body weight is significantly lower than that in control mice

cardiovascular system

increased heart weight ( J:265839 )

• at 4 weeks of age, heart weight-to-body weight ratio is significantly higher than that in control mice

dilated cardiomyopathy ( J:265839 )

• mice exhibit severe dilated cardiomyopathy, as determined by increased heart size, histology, and echocardiography

• in contrast, skeletal muscle shows no dramatic defects

decreased cardiac muscle contractility ( J:265839 )

• mice show a significant decrease in fractional shortening (%) at 4 weeks of age

abnormal heart echocardiography feature ( J:265839 )

• at 4 weeks of age, LVEDD (left ventricular end diastolic diameter) and LVESD (left ventricular end systolic diameter) are significantly increased whereas IVDS (intraventricular septum in diastole) and IVSS (intraventricular septum in systole) are significantly decreased relative to those in control mice

• however, LVDPW (left ventricular posterior wall in diastole), LVSPW (left ventricular posterior wall in systole) and heart rate remain relatively normal

cellular

cellular phenotype ( J:265839 )

N • at 4 weeks of age, hearts show no significant changes in mitochondrial and nuclear DNA levels

abnormal cell physiology ( J:265839 )

• impaired nuclear tRNA processing causes imbalanced levels of regulatory noncoding RNAs

abnormal mitochondrial physiology ( J:265839 )

• heart mitochondria from 4-week-old mice show impaired 3 tRNA processing and severe mitochondrial dysfunction through impaired OXPHOS biogenesis and oxygen consumption

• loss of 3' tRNA processing results in impaired mitochondrial ribosome assembly

abnormal oxidative phosphorylation ( J:265839 )

• impaired OXPHOS biogenesis results in a significant reduction in mitochondrial oxygen consumption in the non-phosphorylated, phosphorylated, and uncoupled respiration state of all three proton-pumping complexes

abnormal mitochondrial ATP synthesis coupled electron transport ( J:265839 )

• heart mitochondria show a profound reduction in mitochondrial respiration at complex I, II-III, and IV relative to controls

abnormal translation ( J:265839 )

• heart mitochondria from 4-week-old mice show a significant reduction in protein synthesis of all mitochondrially encoded proteins

• reduced nuclear tRNA levels result in a ~50% reduction in cytoplasmic protein synthesis because of reduced polysome formation

homeostasis/metabolism

abnormal translation ( J:265839 )

• heart mitochondria from 4-week-old mice show a significant reduction in protein synthesis of all mitochondrially encoded proteins

• reduced nuclear tRNA levels result in a ~50% reduction in cytoplasmic protein synthesis because of reduced polysome formation

muscle

dilated cardiomyopathy ( J:265839 )

• mice exhibit severe dilated cardiomyopathy, as determined by increased heart size, histology, and echocardiography

• in contrast, skeletal muscle shows no dramatic defects

decreased cardiac muscle contractility ( J:265839 )

• mice show a significant decrease in fractional shortening (%) at 4 weeks of age

Genotype
MGI:6282903

cn99

• Allelic Composition: Prorp^tm1.1Afi/Prorp^tm1.1Afi; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N * FVB

mortality/aging

premature death ( J:238964 )

• mice die by 11 weeks of age

cardiovascular system

myocardium necrosis ( J:238964 )

• peaking at 11 weeks

increased heart weight ( J:238964 )

• relative to body weight, at weeks 4, 8 and 11

cardiomyopathy ( J:238964 )

• with increased heart weight, accumulation of necrotic foci in the myocardium and mitochondrial dysfunction

cellular

myocardium necrosis ( J:238964 )

• peaking at 11 weeks

abnormal mitochondrial physiology ( J:238964 )

• peaking at 11 weeks, with reduced complex I and complex IV staining in muscles

• impaired tRNA 5 end processing in heart mitochondria

abnormal mitochondrial ATP synthesis coupled electron transport ( J:238964 )

• reduced respiratory supercomplexes due to reduced biogenesis and stability

muscle

myocardium necrosis ( J:238964 )

• peaking at 11 weeks

cardiomyopathy ( J:238964 )

• with increased heart weight, accumulation of necrotic foci in the myocardium and mitochondrial dysfunction

growth/size/body

increased heart weight ( J:238964 )

• relative to body weight, at weeks 4, 8 and 11

Genotype
MGI:6856855

cn100

• Allelic Composition: Rexo2^tm1.1Arte/Rexo2^tm1.1Arte; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N * FVB

normal phenotype

no abnormal phenotype detected ( J:282882 )

• mice are viable and healthy at 52 weeks of age, showing no obvious phenotype

Genotype
MGI:6360162

cn101

• Allelic Composition: Tefm^tm1.1Lrsn/Tefm^tm1.1Lrsn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N * FVB

mortality/aging

premature death ( J:276874 )

• maximal longevity of 9 weeks

cardiovascular system

abnormal myocardial fiber morphology ( J:276874 )

• disrupted mitochondrial alignment and disorganized cristae with a 1.5-fold increase in mitochondrial mass and mtDNA

enlarged heart ( J:276874 )

increased heart weight ( J:276874 )

growth/size/body

enlarged heart ( J:276874 )

increased heart weight ( J:276874 )

decreased body weight ( J:276874 )

cellular

abnormal mitochondrial morphology ( J:276874 )

• disrupted mitochondrial alignment and disorganized cristae with a 1.5-fold increase in mitochondrial mass and mtDNA in the heart

increased mitochondrial DNA content ( J:276874 )

• in the heart

abnormal mitochondrial ATP synthesis coupled electron transport ( J:276874 )

• reduced OXPHOS capacity in the heart

muscle

abnormal myocardial fiber morphology ( J:276874 )

• disrupted mitochondrial alignment and disorganized cristae with a 1.5-fold increase in mitochondrial mass and mtDNA

Genotype
MGI:6147657

cn102

• Allelic Composition: Polrmt^tm1.1Arte/Polrmt^tm1.1Arte; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N * FVB

mortality/aging

premature death ( J:258184 )

• all die before 6 weeks of age

cardiovascular system

dilated heart left ventricle ( J:258184 )

dilated cardiomyopathy ( J:258184 )

• progressive enlargement of the heart with dilation of the left ventricular chamber

decreased heart rate variability ( J:258184 )

• 40% reduction in heart rate variability in older mice

cellular

abnormal mitochondrial morphology ( J:258184 )

• disorganized cristae

abnormal mitochondrial physiology ( J:258184 )

• severe mitochondrial dysfunction in the heart of terminal stage mice

muscle

dilated cardiomyopathy ( J:258184 )

• progressive enlargement of the heart with dilation of the left ventricular chamber

Genotype
MGI:5427444

cn103

• Allelic Composition: Pik3c3^{tm1c(EUCOMM)Wtsi}/Pik3c3^{tm1c(EUCOMM)Wtsi}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6N * FVB/N

Cardiac dysfunction in Pik3c3^{tm1c(EUCOMM)Wtsi}/Pik3c3^{tm1c(EUCOMM)Wtsi} Tg(Ckmm-cre)5Khn/0 mice

mortality/aging

premature death ( J:182628 )

• mice die between 5 and 13 weeks of age

cardiovascular system

abnormal heart morphology ( J:182628 )

• hearts exhibit disorganized mitochondria and Z-lines with increased number of small-sized mitochondria and enlarged vacuoles compared with control hearts

enlarged heart ( J:182628 )

increased heart weight ( J:182628 )

abnormal heart left ventricle morphology ( J:182628 )

• mice exhibit an increased in left ventricular wall thickness and mass compared with control mice

increased heart left ventricle weight ( J:182628 )

decreased cardiac muscle contractility ( J:182628 )

• decreased cardiac contractility with lower ejection fraction and fractional shortening compared with control mice

congestive heart failure ( J:182628 )

muscle

decreased cardiac muscle contractility ( J:182628 )

• decreased cardiac contractility with lower ejection fraction and fractional shortening compared with control mice

growth/size/body

enlarged heart ( J:182628 )

increased heart weight ( J:182628 )

Genotype
MGI:6151396

cn104

• Allelic Composition: Mgme1^tm1.1Lrsn/Mgme1^tm1.1Lrsn; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6NTac * FVB

cellular

decreased mitochondrial DNA content ( J:259702 )

• depletion and deletion

Genotype
MGI:6444640

cn105

• Allelic Composition: Fis1^tm1.1Itl/Fis1^tm1.1Itl; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: C57BL/6NTac * FVB

homeostasis/metabolism

impaired exercise endurance ( J:290485 )

• following 3 consecutive days of exercise to exhaustion, mice exhibit increased body temperature, increased plasma cytokines (IL-6, IL-12p40, IL-13, KC, RANTES and IFNbeta), disorganized Z-band in soleus muscle, and delayed onset muscle ultrastructure change in soleus muscle compared with wild-type mice

• however, plasma cytokine levels return to normal after exercise exhaustion

increased circulating interferon-beta level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

increased circulating interleukin-12b level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

increased circulating interleukin-13 level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

increased circulating interleukin-6 level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

increased body temperature ( J:290485 )

• following 3 consecutive days of exercise to exhaustion

cellular

abnormal mitochondrial crista morphology ( J:290485 )

• loss of cristae and low matric density

increased mitochondrial size ( J:290485 )

• prior to and after exercise

abnormal mitochondrial physiology ( J:290485 )

• impaired respiratory chain function in slow muscle with reduced Complex I protein levels

muscle

abnormal Z line morphology ( J:290485 )

• in the soleus of mice exercised to exhausting on consecutive days

abnormal skeletal muscle morphology ( J:290485 )

• delayed onset muscle ultrastructure change in the soleus of mice exercised to exhausting on consecutive days

• however, there are no ultrastructure changes in the gastrocnemius following exercise

behavior/neurological

impaired exercise endurance ( J:290485 )

• following 3 consecutive days of exercise to exhaustion, mice exhibit increased body temperature, increased plasma cytokines (IL-6, IL-12p40, IL-13, KC, RANTES and IFNbeta), disorganized Z-band in soleus muscle, and delayed onset muscle ultrastructure change in soleus muscle compared with wild-type mice

• however, plasma cytokine levels return to normal after exercise exhaustion

immune system

increased circulating interferon-beta level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

increased circulating interleukin-12b level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

increased circulating interleukin-13 level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

increased circulating interleukin-6 level ( J:290485 )

• in mice exercised to exhausting on consecutive days

• however, plasma cytokine levels return to normal after exercise exhaustion

Genotype
MGI:5762817

cn106

• Allelic Composition: Appl2^tm1Smoc/Appl2^tm1Smoc; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: FVB

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:230004 )

N • mice exhibit normal fasting glucose and insulin levels

improved glucose tolerance ( J:230004 )

• in response to glucose challenge

increased insulin sensitivity ( J:230004 )

• determined by insulin tolerance testing

muscle

increased muscle cell glucose uptake ( J:230004 )

• increased glucose uptake in extensor digitorum longus or soleus muscles compared with control muscles

behavior/neurological

behavior/neurological phenotype ( J:230004 )

N • mice exhibit normal food intake

growth/size/body

growth/size/body region phenotype ( J:230004 )

N • mice exhibit normal body weight

cellular

increased muscle cell glucose uptake ( J:230004 )

• increased glucose uptake in extensor digitorum longus or soleus muscles compared with control muscles

Genotype
MGI:5907999

cn107

• Allelic Composition: Sod2^tm1Shs/Sod2^tm1Shs; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: FVB

cardiovascular system

myocardial fiber degeneration ( J:171017 )

• left ventricle wall shows myocardial degeneration

• treatment with EUK-8, a superoxide dismutase and catalase mimetic, diminishes myocardial degeneration

myocardial fiber disarray ( J:171017 )

• left ventricle wall shows myocyte disarray

• EUK-8 treated mice show diminished myocyte disarray

increased heart weight ( J:171017 )

• progressively increasing heart-to-body weight ratio

• treatment with EUK-8, a superoxide dismutase and catalase mimetic, decreases heart weight

cardiac interstitial fibrosis ( J:171017 )

• diffuse fibrotic scars surrounding myocardial cells

• EUK-8 treated mice show diminished fibrosis

dilated heart ( J:171017 )

• heart dilatation

dilated heart left ventricle ( J:171017 )

• increase in left ventricular end-diastolic internal dimension (LVIDd)

• EUK-8 treatment for 4 weeks decreases LVIDd

dilated cardiomyopathy ( J:171017 )

abnormal heart echocardiography feature ( J:171017 )

• increase in left ventricular end-diastolic internal dimension (LVIDd)

• EUK-8 treatment for 4 weeks decreases LVIDd

growth/size/body

increased heart weight ( J:171017 )

• progressively increasing heart-to-body weight ratio

• treatment with EUK-8, a superoxide dismutase and catalase mimetic, decreases heart weight

cellular

cardiac interstitial fibrosis ( J:171017 )

• diffuse fibrotic scars surrounding myocardial cells

• EUK-8 treated mice show diminished fibrosis

oxidative stress ( J:171017 )

• heart tissue exhibits oxidative DNA damage

• EUK-8 treatment attenuates oxidative DNA damage in heart tissue

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:171017 )

• telomerase activity is decreased in heart tissues, however telomere length is normal

• EUK-8 treatment restores normal telomerase activity

muscle

myocardial fiber degeneration ( J:171017 )

• left ventricle wall shows myocardial degeneration

• treatment with EUK-8, a superoxide dismutase and catalase mimetic, diminishes myocardial degeneration

myocardial fiber disarray ( J:171017 )

• left ventricle wall shows myocyte disarray

• EUK-8 treated mice show diminished myocyte disarray

dilated cardiomyopathy ( J:171017 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:171017
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:171017

Genotype
MGI:3580297

cn108

• Allelic Composition: Stk11^tm1Keis/Stk11^tm1Keis; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: FVB

muscle

decreased muscle cell glucose uptake ( J:98513 )

• block of glucose uptake stimulated by 5-aminoimidazole-4-caroboxamide (AICAR) or by muscle contraction, but not by insulin

• possessed normal fasted and fed blood glucose levels

reproductive system

male infertility ( J:98513 )

♂ • homozygous male mice are infertile, female are fertile

growth/size/body

growth/size/body region phenotype ( J:98513 )

N • normal growth from 4 to 10 weeks of age

cellular

decreased muscle cell glucose uptake ( J:98513 )

• block of glucose uptake stimulated by 5-aminoimidazole-4-caroboxamide (AICAR) or by muscle contraction, but not by insulin

• possessed normal fasted and fed blood glucose levels

Genotype
MGI:3848249

cn109

• Allelic Composition: Plrg1^tm2Jcbr/Plrg1^tm2Jcbr; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: FVB

mortality/aging

premature death ( J:149153 )

• survival at P28 is 5% compared to 80% for wild-type mice

cardiovascular system

abnormal heart ventricle morphology ( J:149153 )

• at P24, both ventricles exhibit atrophy unlike in wild-type mice

thin ventricular wall ( J:149153 )

dilated heart ( J:149153 )

dilated heart left ventricle ( J:149153 )

• at P24

dilated heart right ventricle ( J:149153 )

• at P24

dilated cardiomyopathy ( J:149153 )

decreased ventricle muscle contractility ( J:149153 )

increased cardiomyocyte apoptosis ( J:149153 )

muscle

dilated cardiomyopathy ( J:149153 )

decreased ventricle muscle contractility ( J:149153 )

increased cardiomyocyte apoptosis ( J:149153 )

cellular

increased cardiomyocyte apoptosis ( J:149153 )

Genotype
MGI:2651647

cn110

• Allelic Composition: Ttn^tm1Her/Ttn^tm1Her; Tg(Ckmm-cre)5Khn/0
• Genetic Background: Not Specified

mortality/aging

premature death ( J:81993 )

• death at about 5 wks of age

behavior/neurological

abnormal posture ( J:81993 )

abnormal gait ( J:81993 )

cardiovascular system

cardiovascular system phenotype ( J:81993 )

N • the heart was reduced in size, but in proportion to reduced overall body size

N • no pathology of the heart was reported

growth/size/body

decreased body size ( J:81993 )

postnatal growth retardation ( J:81993 )

• apparent at 3 wks of age

muscle

abnormal sarcomere morphology ( J:81993 )

• disarrayed sarcomeres, observed in less than 50% of the area of the myocytes

abnormal M line morphology ( J:81993 )

• pale, widened M-lines, devoid of M-line bridges

progressive muscle weakness ( J:81993 )

• resulting in abnormal posture, gait, and blepharoptosis

vision/eye

blepharoptosis ( J:81993 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2J		DOID:0110283	OMIM:608807	J:81993