Phenotypes associated with this allele

• Allele Symbol: Tg(CAG-cre/Esr1*)5Amc
• Allele Name: transgene insertion 5, Andrew P McMahon
• Allele ID: MGI:2182767
• Summary: 152 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	App^tm1.1Tlyp/App^tm1.1Tlyp Tg(CAG-cre/Esr1*)5Amc/?	B6.Cg-App^tm1.1Tlyp Tg(CAG-cre/Esr1*)5Amc	MGI:6114982
cn2	Gt(ROSA)26Sor^tm7(Pik3ca*,EGFP)Rsky/Gt(ROSA)26Sor^+ Tg(CAG-cre/Esr1*)5Amc/0	B6.Cg-Gt(ROSA)26Sor^tm7(Pik3ca*,EGFP)Rsky Tg(CAG-cre/Esr1*)5Amc	MGI:6197269
cn3	Rtn4r^tm2.1Stmr/Rtn4r^tm2.2Stmr Tg(CAG-cre/Esr1*)5Amc/0	B6.Cg-Rtn4r^tm2.1Stmr/Rtn4r^tm2.2Stmr Tg(CAG-cre/Esr1*)5Amc0	MGI:5510953
cn4	Camk2a^tm1.1Yelg/Camk2a^tm1.1Yelg Tg(CAG-cre/Esr1*)5Amc/0	B6J.Cg-Camk2a^tm1.1Yelg Tg(CAG-cre/Esr1*)5Amc	MGI:5795687
cn5	Npc1^m1N/Npc1^tm1.1Apl Tg(CAG-cre/Esr1*)5Amc/0	B6J.Cg-Npc1^m1N/Npc1^tm1.1Apl Tg(CAG-cre/Esr1*)5Amc	MGI:5925342
cn6	Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^tm7(SMO*/YFP)Amc Tg(CAG-cre/Esr1*)5Amc/0	chimera involves: 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA * Swiss Webster	MGI:4839957
cn7	Gnl3^tm2.1Rylt/Gnl3^tm2.1Rylt Trp53^tm1Tyj/Trp53^tm1Tyj Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * 129S2/SvPas * C57BL/6 * CBA	MGI:5523425
cn8	Gnl3^tm2.1Rylt/Gnl3^tm2.1Rylt Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * 129S2/SvPas * C57BL/6 * CBA	MGI:5523423
cn9	Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6	MGI:5824831
cn10	Avpr2^tm2.1Jwe/Y Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6	MGI:7282305
cn11	Tbx3^tm3.1Moon/Tbx3^tm3.1Moon Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6	MGI:5538607
cn12	Seh1l^tm1Lzha/Seh1l^tm1Lzha Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA	MGI:6712827
cn13	Dicer1^tm1Bdh/Dicer1^tm1Bdh Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA	MGI:6449234
cn14	Hap1^tm2Xjl/Hap1^tm2Xjl Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA	MGI:5691394
cn15	Pax3^tm1.1Sjc/Pax3^tm1.1Sjc Pax7^tm1.2Fan/Pax7^tm1.2Fan Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:4353177
cn16	Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:4834592
cn17	Tardbp^tm1.1Pcw/Tardbp^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:4834589
cn18	Sox4^tm1Vlf/Sox4^tm1Vlf Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:3773016
cn19	Cdk1^tm2.1Kald/Cdk1^tm2.1Kald Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:5318110
cn20	Celf4^tm1.1Frk/Celf4^tm1.1Frk Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6J	MGI:6194636
cn21	Tg(CAG-cre/Esr1*)5Amc/0 Ube3a^tm1Yelg/Ube3a^+	involves: 129P2/OlaHsd * 129S2/SvPasCrl * C57BL/6J	MGI:5704117
cn22	Lhx2^tm1Monu/Lhx2^tm1Dra Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA	MGI:4453346
cn23	Lhx2^tm1Monu/Lhx2^tm1Monu Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA	MGI:4453348
cn24	Supv3l1^tm2.1Jkl/Supv3l1^tm2.2Jkl Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:3833891
cn25	St14^tm2Bug/St14^tm3Bug Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * CBA	MGI:4361221
cn26	Supv3l1^tm2Jkl/Supv3l1^tm2Jkl Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3833890
cn27	Mcat^tm1.1Ssmi/Mcat^tm1.1Ssmi Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA	MGI:5466536
cn28	Nrg1^tm3Cbm/Nrg1^tm3Cbm Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5524264
cn29	Mecp2^tm2Bird/Y Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3832684
cn30	Reck^tm1Ito/Reck^tm1.1Noda Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:4830343
cn31	Mecp2^tm2Bird/Mecp2^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3712287
cn32	Ppp2r1a^tm1.1Wltr/Ppp2r1a^tm1.2Wltr Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129S4/SvJaeSor * C57BL/6 * CBA * FVB/NCrl	MGI:5287435
cn33	Dohh^tm1.1Sbal/Dohh^tm1.1Sbal Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ	MGI:5903288
cn34	Bub1^tm1Ssta/Bub1^tm1.1Ssta Tg(CAG-cre/Esr1*)5Amc/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3767640
cn35	Inpp5e^tm1.1Ssch/Inpp5e^tm1.2Ssch Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4360189
cn36	Dscam^tm1Pfu/Dscam^tm1Pfu Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5305034
cn37	Bub1^tm1Ssta/Bub1^tm1Ssta Tg(CAG-cre/Esr1*)5Amc/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3767641
cn38	Edn2^tm1.1Nat/Edn2^tm1.1Nat Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4438398
cn39	Sdhd^tm1Jlob/Sdhd^tm2Jlob Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5438129
cn40	Kcnq1ot1^tm2.1Ckan/Kcnq1ot1^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SD7	MGI:5431829
cn41	Numa1^tm1.1Dwc/Numa1^tm1.1Dwc Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL	MGI:3838126
cn42	Htt^tm1Mem/Htt^tm6Mem Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * Swiss Webster	MGI:7266814
cn43	Pnkp^tm1.1Pmc/Pnkp^tm1.1Pmc Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:5795834
cn44	Gls^tm2.1Sray/Gls^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:5784520
cn45	Ate1^tm1Avar/Ate1^tm2.1Avar Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:4415303
cn46	Gdnf^tm1Bbd/Gdnf^tm1Jlob Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:3809283
cn47	Rapgef2^tm1.1Hous/Rapgef2^tm1.1Hous Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:4839181
cn48	Wnt5a^tm1.1Tpy/Wnt5a^tm1.1Tpy Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:5440734
cn49	Six3^tm2Gco/Six3^tm2.1Gco Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:3693848
cn50	Kmt5a^tm1.1Dare/Kmt5a^tm1.2Dare Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/Sv * C57BL/6 * CBA * SJL	MGI:3842509
cn51	Mecom^tm1Aspe/Mecom^tm2.1Aspe Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/SvImJ * C57BL/6 * C57BL/6J * CBA	MGI:5301413
cn52	Mecom^tm2.1Aspe/Mecom^tm2.1Aspe Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S1/SvImJ * C57BL/6 * CBA	MGI:5301414
cn53	Cxadr^tm1.1Ics/Cxadr^tm1.1Ics Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * C57BL/6J * CBA	MGI:5086257
cn54	Syngap1^tm2Geno/Syngap1^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:5469879
cn55	Alkbh4^tm1Geno/Alkbh4^tm1Geno Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:5549958
cn56	Atr^tm2Bal/Atr^tm2Bal Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:5316225
cn57	Ccnd1^tm1Wbg/Ccnd1^tm5.1Pisc Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:5468350
cn58	Ccnd1^tm1Wbg/Ccnd1^tm5.1Pisc Tg(CAG-cre/Esr1*)5Amc/0 Tg(MMTV-Erbb2)NK1Mul/0	involves: 129S2/SvPas * C57BL/6 * CBA * FVB/N	MGI:5468352
cn59	Esco2^tm1.1Ge/Esco2^tm1.1Ge Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * CBA * SJL	MGI:5308067
cn60	Kdm6a^tm1Cdcn/Y Tg(CAG-cre/Esr1*)5Amc/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6J * CBA * FVB/N	MGI:6192377
cn61	Cdc73^tm1Btt/Cdc73^tm1Btt Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:3795455
cn62	Trpm7^tm1Clph/Trpm7^tm1Clph Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:6220878
cn63	Lhx2^tm1.1Lcar/Lhx2^tm1Dra Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:4453345
cn64	Nrl^tm1Jcco/Nrl^tm1Jcco Rho^tm1Jlem/Rho^tm1Jlem Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:5490597
cn65	Pomc^tm2Low/Pomc^tm2Low Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:5473527
cn66	Lhx2^tm1.1Lcar/Lhx2^tm1.1Lcar Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:4453347
cn67	Mmp14^tm1Hbh/Mmp14^tm1.1Khol Mmp15^tm1Kohl/Mmp15^tm1Kohl Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA	MGI:4868430
cn68	Pappa^tm1Lex/Pappa^tm1Lex Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S5/SvEvBrd * C57BL/6 * CBA	MGI:5523415
cn69	Egln1^tm1Kael/Egln1^tm1Kael Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:3793292
cn70	Ewsr1^tm1Sblee/Ewsr1^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:4429150
cn71	Ewsr1^tm2(FLI1*)Sblee/Ewsr1^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:4429149
cn72	Kdm5a^tm1Kael/Kdm5a^tm1Kael Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:5296661
cn73	Ptpn11^tm6Bgn/Ptpn11^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:3845013
cn74	Tg(CAG-cre/Esr1*)5Amc/0 Wee1^tm1Cxd/Wee1^tm1Cxd	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:5707476
cn75	Gak^tm2Legr/Gak^tm2Legr Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:5305780
cn76	Tg(CAG-cre/Esr1*)5Amc/0 Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:5688888
cn77	Ccn2^tm2Mae/Ccn2^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:4838161
cn78	Sav1^tm1.1Rjo/Sav1^tm1.1Rjo Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * CD-1 * SJL	MGI:4430543
cn79	Mdm4^tm3Glo/Mdm4^tm3.1Glo Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N	MGI:5142305
cn80	Hdac3^tm1Swh/Hdac3^tm1.1Swh Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N	MGI:3795942
cn81	Ift20^tm1.1Gjp/Ift20^tm1.2Gjp Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * CBA	MGI:6383666
cn82	Myog^tm3Whk/Myog^tm3Whk Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3620012
cn83	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:6404152
cn84	Dicer1^tm1Snj/Dicer1^tm1Snj Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3809305
cn85	Tbx1^tm1Bld/Tbx1^tm3Bld Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:4453459
cn86	Lmx1b^tm1Rjo/Lmx1b^tm4.1Rjo Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:4818573
cn87	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:4941477
cn88	Trp53^tm1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:5000506
cn89	Trp53^tm3.1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:5000509
cn90	Mstn^tm1Swel/Mstn^tm1Swel Tg(CAG-cre/Esr1*)5Amc/?	involves: 129S7/SvEvBrd-Hprt1 * C57BL/6 * CBA	MGI:3711528
cn91	Ret^tm2(RET)Heno/Ret^tm2(RET)Jmi Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S/Sv * C57BL/6 * CBA	MGI:4820814
cn92	Ret^tm2(RET)Heno/Ret^tm1Cos Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S/Sv * C57BL/6 * CBA	MGI:4820805
cn93	Plxnd1^tm1.1Tmj/Plxnd1^tm1.1Tmj Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * CBA	MGI:3848824
cn94	Tbp^tm1Xjl/Tbp^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S/SvEv * C57BL/6 * CBA	MGI:5693885
cn95	Fktn^tm1Kcam/Fktn^tm1Kcam Tg(CAG-cre/Esr1*)5Amc/?	involves: 129S/SvEv * C57BL/6 * CBA	MGI:5435674
cn96	Pou4f2^tm4(DTA)Whk/Pou4f2^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S/SvEv * C57BL/6 * CBA	MGI:3838797
cn97	Tg(CAG-Bgeo/Lhx2,-GFP)#Lcar/0 Tg(CAG-cre/Esr1*)5Amc/0	involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * CBA	MGI:4453351
cn98	Rab35^tm1.1Vha/Rab35^tm1.1Vha Tg(CAG-cre/Esr1*)5Amc/0	involves: 129/Sv * 129S4/SvJaeSor * C57BL/6J * C57BL/6 * CBA	MGI:6467551
cn99	Nlrp3^tm1Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850050
cn100	Nlrp3^tm2Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850052
cn101	Tg(CAG-cre/Esr1*)5Amc/? Thra^tm1Ffla/Thra^+	involves: 129/Sv * C57BL/6 * CBA	MGI:3758925
cn102	Foxn1^tm1.1Dmsu/Foxn1^tm1.1Dmsu Tg(CAG-cre/Esr1*)5Amc/0	involves: 129/Sv * C57BL/6 * CBA * SJL	MGI:4454657
cn103	Foxn1^nu/Foxn1^tm1.1Dmsu Tg(CAG-cre/Esr1*)5Amc/0	involves: 129/Sv * C57BL/6 * CBA * SJL	MGI:4454658
cn104	Gfra1^tm1Jmi/Gfra1^tm2Jmi Tg(CAG-cre/Esr1*)5Amc/0	involves: 129/Sv * C57BL/6 * CBA * SJL	MGI:3715267
cn105	Trip11^tm1.1Psmi/Trip11^tm1.2Psmi Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/? Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * SJL/J	MGI:6154270
cn106	Tmem30a^tm1.1Xjz/Tmem30a^tm1.1Xjz Tg(CAG-cre/Esr1*)5Amc/0	involves: 129/SvEv * C57BL/6 * CBA	MGI:6382630
cn107	Epas1^tm1Mcs/Epas1^tm1.1Mcs Tg(CAG-cre/Esr1*)5Amc/0	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:6724166
cn108	Bax^tm1Sjk/Bax^tm1Sjk Ret^tm1Heno/Ret^tm3.1(Bcl2l1)Heno Tg(CAG-cre/Esr1*)5Amc/0	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:4459062
cn109	Ret^tm1Heno/Ret^tm3.1(Bcl2l1)Heno Tg(CAG-cre/Esr1*)5Amc/0	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:4459061
cn110	Ret^tm1Heno/Ret^tm2(RET)Heno Tg(CAG-cre/Esr1*)5Amc/0	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:4459060
cn111	Gt(ROSA)26Sor^tm1(Smo/EYFP)Amc/? Tg(CAG-cre/Esr1*)5Amc/?	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:3716204
cn112	Wnt9b^tm1.1Amc/Wnt9b^tm1.2Amc Tg(CAG-cre/Esr1*)5Amc/0	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:5428000
cn113	Cxcl12^tm1.1Ystz/Cxcl12^tm1.2Ystz Tg(CAG-cre/Esr1*)5Amc/0	involves: 129X1/SvJ * C57BL/6 * CBA * FVB/N	MGI:4888376
cn114	Nr1d1^tm1.1Rev/Nr1d1^tm1.1Rev Nr1d2^tm1.1Rev/Nr1d2^tm1.1Rev Tg(CAG-cre/Esr1*)5Amc/0	involves: BALB/cJ * C57BL/6 * C57BL/6J * CBA	MGI:5426706
cn115	Pml^tm1(PML/RARA)Ley/Pml^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: BALB/cJ * C57BL/6 * CBA	MGI:5014087
cn116	Pou4f1^tm1.1Gan/Pou4f1^tm1.1Gan Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * C57BL/6J * CBA	MGI:5607142
cn117	Pou4f2^tm2.1Gan/Pou4f2^tm2.1Gan Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * C57BL/6J * CBA	MGI:5607145
cn118	Cop1^tm1.1Vmd/Cop1^tm2.1Vmd Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * C57BL/6N * CBA	MGI:5013602
cn119	Sel1l^tm1c(KOMP)Wtsi/Sel1l^tm1c(KOMP)Wtsi Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * C57BL/6N * CBA * SJL	MGI:5581523
cn120	Cemip2^tm1.1Cya/Cemip2^tm1.1Cya Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:7616226
cn121	Aqp2^tm1Bxy/Aqp2^tm1Bxy Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:3653933
cn122	Nr2e1^tm1Rev/Nr2e1^tm1Rev Tg(CAG-cre/Esr1*)5Amc/?	involves: C57BL/6 * CBA	MGI:3777343
cn123	Stk3^tm1.1Yy/Stk3^tm1Yy Stk4^tm1.1Yy/Stk4^tm1.1Yy Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:4422186
cn124	Kat7^tm1.1Avo/Kat7^tm1.1Avo Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:4947714
cn125	Map2k7^tm1Rjd/Map2k7^tm1Rjd Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5297907
cn126	Map2k4^tm1Ctr/Map2k4^tm1Ctr Map2k7^tm1Rjd/Map2k7^tm1Rjd Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5297908
cn127	Map2k4^tm1Ctr/Map2k4^tm1Ctr Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5297910
cn128	Lbx1^tm1.1Khan/Lbx1^tm1.1Khan Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5304417
cn129	Ccnd3^tm2.1Pisc/Ccnd3^tm2.1Pisc Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5468353
cn130	Nrl^tm1Jcco/Nrl^tm1Jcco Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5490590
cn131	Map3k12^tm1Lewc/Map3k12^tm1Lewc Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5502227
cn132	Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5552951
cn133	Ino80^tm1Schg/Ino80^tm1Schg Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5898009
cn134	Gt(ROSA)26Sor^tm1(CAG-MFN2*T105M)Dple/Gt(ROSA)26Sor^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:6198665
cn135	Nup85^tm1.1Yter/Nup85^tm1.1Yter Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:6451097
cn136	Tcfl5^tm1Frem/Tcfl5^tm1Frem Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:7316744
cn137	Tg(CAG-cre/Esr1*)5Amc/0 Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0	involves: C57BL/6 * CBA * DBA/2	MGI:3821885
cn138	Prom1^tm1.1(DTA)Toko/Prom1^tm1.1(DTA)Toko Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA * SJL	MGI:4360394
cn139	Abcg5^tm1.1Hobb/Abcg5^tm1.1Hobb Abcg8^tm1.1Hobb/Abcg8^tm1.1Hobb Tg(CAG-cre/Esr1*)5Amc/?	involves: C57BL/6 * CBA * SJL	MGI:5607628
cn140	Nkx2-5^tm1.1Gum/Nkx2-5^tm1.1Gum Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J	MGI:5810739
cn141	Dhps^tm2c(EUCOMM)Wtsi/Dhps^tm2c(EUCOMM)Wtsi Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J * C57BL/6N * CBA * SJL	MGI:5903287
cn142	Atg7^tm1Tchi/Atg7^tm1Tchi Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj	MGI:6870515
cn143	Kdm6a^tm1Cdcn/Kdm6a^tm1Cdcn Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J * CBA	MGI:6192376
cn144	Emc3^em1Xjz/Emc3^em1Xjz Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J * CBA	MGI:6376225
cn145	Kdm6a^tm1Cdcn/Y Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J * CBA	MGI:6192375
cn146	Fam210a^tm1c(EUCOMM)Wtsi/Fam210a^tm1c(EUCOMM)Wtsi Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6N * CBA * SJL	MGI:6159281
cn147	Pou4f1^tm1.1Gan/Pou4f1^tm1.1Gan Pou4f2^tm2.1Gan/Pou4f2^tm2.1Gan Tg(CAG-cre/Esr1*)5Amc/0	Not Specified	MGI:5607147
cx148	Syngap1^tm2Geno/Syngap1^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:5469878
cx149	Nlrp3^tm2Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850051
cx150	Nlrp3^tm1Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850049
tg151	Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:3845073
tg152	Tg(CAG-cre/Esr1*)5Amc/?	involves: C57BL/6 * CBA	MGI:3716206

Genotype
MGI:6114982

cn1

• Allelic Composition: App^tm1.1Tlyp/App^tm1.1Tlyp; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: B6.Cg-App^tm1.1Tlyp Tg(CAG-cre/Esr1*)5Amc

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

nervous system

abnormal stratification in cerebral cortex ( J:241006 )

• in a subset of embryos, some TBR1+ cells (expressed in the lower cortical layer) are observed below the cortical plate after tamoxifen treatment

• following tamoxifen treatment, the majority of Reelin+ cells (expressed in the marginal zone) in some embryonic brains are displaced below the cortical plate, and, in other brains, Reelin+ cells are displaced to the intermediate zone

• number and morphology of astrocytes and microglia are similar to wild-type in the hippocampus and cerebral cortex following tamoxifen treatment at E12, 13, and 14 (harvested on E18)

Genotype
MGI:6197269

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm7(Pik3ca*,EGFP)Rsky}/Gt(ROSA)26Sor⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm7(Pik3ca*,EGFP)Rsky} Tg(CAG-cre/Esr1*)5Amc

mortality/aging

premature death ( J:264410 )

• mice administered a single low dose (4 mg/kg) of tamoxifen to induce cre recombination survive 2 months and then die with multiple abnormalities

• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization

postnatal lethality, incomplete penetrance ( J:264410 )

• mice start to rapidly die after 40 mg/kg tamoxifen administration, with 50% of mortality at day 9

• tamoxifen-administered mice treated with BYL719 are alive after 40 days, however interruption of BYL719 treatment 40 days after tamoxifen-administration leads to rapid death

• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization

growth/size/body

kidney cyst ( J:264410 )

• kidney cysts in tamoxifen-administered mice

visceromegaly ( J:264410 )

• organomegaly is seen in mice administered a single low dose of tamoxifen

cardiovascular system

abnormal blood vessel morphology ( J:264410 )

• vessel abnormalities in tamoxifen-administered mice

• tamoxifen-administered mice treated with BYL719 show normal vessels

abnormal vein morphology ( J:264410 )

• ecstatic venous channels with a thin endothelial cell lining, surrounded by sparse, erratically distributed vascular smooth muscle cells and a disorganized extracellular matrix are seen in mice administered a low dose of tamoxifen

dilated vasculature ( J:264410 )

• severe vessel dilation in tamoxifen-administered mice

internal hemorrhage ( J:264410 )

• intra-abdominal hemorrhages in tamoxifen-administered mice

liver hemorrhage ( J:264410 )

• hepatic hemorrhages in tamoxifen-administered mice

cellular

increased cell proliferation ( J:264410 )

• high number of proliferating cells in affected organs of tamoxifen-administered mice

• however, no changes in apoptosis are seen

• tamoxifen-administered mice treated with BYL719 show a reduction in proliferation

hematopoietic system

abnormal spleen morphology ( J:264410 )

• loss of spleen microarchitecture integrity in tamoxifen-administered mice

immune system

abnormal spleen morphology ( J:264410 )

• loss of spleen microarchitecture integrity in tamoxifen-administered mice

enlarged lymphatic vessel ( J:264410 )

• expansion of lymphatic vessels in tamoxifen-administered mice

limbs/digits/tail

abnormal limb morphology ( J:264410 )

• mice administered a single low dose of tamoxifen progressively develop asymmetrical overgrowth of extremities, disseminated voluminous tumors and subcutaneous vascular abnormalities

• low-dose tamoxifen administered mice treated with BYL719 show improvement of the overgrowth of extremities, however, withdrawal of BYL719 leads to the development of asymmetric extremity hypertrophy within 4 weeks

liver/biliary system

liver hemorrhage ( J:264410 )

• hepatic hemorrhages in tamoxifen-administered mice

hepatic steatosis ( J:264410 )

• severe liver steatosis with vessel disorganization in tamoxifen-administered mice

muscle

skeletal muscle hypertrophy ( J:264410 )

• muscle hypertrophy in tamoxifen-administered mice

• mice treated with BYL719 7 days after cre induction show improved muscle hypertrophy

neoplasm

increased classified tumor incidence ( J:264410 )

• low dose tamoxifen-administered mice develop tumors that are lipomatous tumors and severe vascular lesions mixing venous and arterial vessels

• low-dose tamoxifen administered mice treated with BYL719 show reduced and disappearance of visible tumors within 2 weeks

• withdrawal of BYL719 from the low-dose tamoxifen administered mice leads to recurrence of tumors

• low-dose tamoxifen-administered mice treated with rapamycin show no effect on tumor growth

renal/urinary system

kidney cyst ( J:264410 )

• kidney cysts in tamoxifen-administered mice

renal fibrosis ( J:264410 )

• fibrosis of the kidney with aberrant vessels in tamoxifen-administered mice

skeleton

scoliosis ( J:264410 )

• scoliosis in tamoxifen-administered mice

• mice treated with BYL719 7 days after cre induction show improved scoliosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CLOVES syndrome		DOID:0080351	OMIM:612918	J:264410

Genotype
MGI:5510953

cn3

• Allelic Composition: Rtn4r^tm2.1Stmr/Rtn4r^tm2.2Stmr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: B6.Cg-Rtn4r^tm2.1Stmr/Rtn4r^tm2.2Stmr Tg(CAG-cre/Esr1*)5Amc0

nervous system

abnormal nervous system regeneration ( J:201118 )

• after optic nerve crush, tamoxifen-treated mice exhibit stronger axonal regeneration compared with control mice though not as complete as in constitutive knock-out mice

• after spinal cord dorsal hemisection injury, tamoxifen-treated mice exhibit improvement of motor function and 5HT fiber density compared with control mice

• however, untreated mice exhibit normal regeneration

Genotype
MGI:5795687

cn4

• Allelic Composition: Camk2a^tm1.1Yelg/Camk2a^tm1.1Yelg; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: B6J.Cg-Camk2a^tm1.1Yelg Tg(CAG-cre/Esr1*)5Amc

behavior/neurological

impaired contextual conditioning behavior ( J:216169 )

• adult mice treated with tamoxifen show severe contextual fear learning deficits relative to control littermates, as revealed by a marked reduction in elicited freezing behavior

impaired spatial learning ( J:216169 )

• in the hidden version of the Morris water maze, adult mice treated with tamoxifen search equally in all four quadrants with no clear preference for the target quadrant during the probe trial, unlike control littermates

• however, no significant differences in latency times to reach the hidden platform, thigmotaxis, swim speed, or path length are observed

nervous system

impaired synaptic plasticity ( J:216169 )

• adult mice treated with tamoxifen exhibit impaired synaptic plasticity

reduced long-term potentiation ( J:216169 )

• adult mice treated with tamoxifen show impaired LTP induction at the CA3-CA1 synapse in the hippocampus in two independent stimulation protocols (100 Hz and theta-burst) relative to control littermates

• however, basal synaptic transmission and paired-pulse facilitation (PPF) are normal

Genotype
MGI:5925342

cn5

• Allelic Composition: Npc1^m1N/Npc1^tm1.1Apl; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: B6J.Cg-Npc1^m1N/Npc1^tm1.1Apl Tg(CAG-cre/Esr1*)5Amc

mortality/aging

premature death ( J:176888 )

• average lifespan is 109 days post tamoxifen injection

nervous system

microgliosis ( J:176888 )

• widespread microgliosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age

increased brain cholesterol level ( J:176888 )

• accumulation of unesterified cholesterol in cerebellar lobule X in tamoxifen-treated mice at 18 weeks of age

Purkinje cell degeneration ( J:176888 )

• progressive anterior-to-posterior Purkinje cell loss in tamoxifen-treated mice

• cells in anterior lobules degenerate early and those in posterior lobules are more resistant to degeneration

astrocytosis ( J:176888 )

• widespread astrocytosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age

abnormal axon morphology ( J:176888 )

• tamoxifen-treated mice exhibit swollen axons in the cortex at 22 weeks of age

axonal spheroids ( J:176888 )

• widespread axonal spheroids in the cerebellum of tamoxifen-treated mice at 18 weeks of age

demyelination ( J:176888 )

• tamoxifen-treated mice exhibit demyelination in the corpus callosum at 22 weeks of age

• widespread secondary demyelination in the cerebellum of tamoxifen-treated mice at 18 weeks of age

behavior/neurological

impaired balance ( J:176888 )

• mice injected with tamoxifen at 6 weeks of age exhibit impaired balance beam performance by 12 weeks which progresses with age

growth/size/body

weight loss ( J:176888 )

• mice injected with tamoxifen at 6 weeks of age start to lose weight around 16 weeks of age

hematopoietic system

microgliosis ( J:176888 )

• widespread microgliosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age

homeostasis/metabolism

increased brain cholesterol level ( J:176888 )

• accumulation of unesterified cholesterol in cerebellar lobule X in tamoxifen-treated mice at 18 weeks of age

immune system

microgliosis ( J:176888 )

• widespread microgliosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Niemann-Pick disease		DOID:14504		J:176888

Genotype
MGI:4839957

cn6

• Allelic Composition: Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^{tm7(SMO*/YFP)Amc}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: chimera involves: 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA * Swiss Webster

nervous system

abnormal brain development ( J:165962 )

• dorsal CNS hyperproliferation at E13.5 after being exposed at E8.5 to tamoxifen

limbs/digits/tail

polydactyly ( J:165962 )

• observed at E13.5 after being exposed at E8.5 to tamoxifen

Genotype
MGI:5523425

cn7

• Allelic Composition: Gnl3^tm2.1Rylt/Gnl3^tm2.1Rylt; Trp53^tm1Tyj/Trp53^tm1Tyj; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * 129S2/SvPas * C57BL/6 * CBA

cellular

abnormal cell physiology ( J:198698 )

• increase in the percentage of MEFs showing signs of replication-induced DNA damage after tamoxifen treatment

abnormal cell death ( J:198698 )

• tamoxifen treatment shortens the lifespan of MEFs

decreased fibroblast proliferation ( J:198698 )

• tamoxifen treatment impairs the long-term proliferative potential of MEFs

Genotype
MGI:5523423

cn8

• Allelic Composition: Gnl3^tm2.1Rylt/Gnl3^tm2.1Rylt; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * 129S2/SvPas * C57BL/6 * CBA

cellular

abnormal cell physiology ( J:198698 )

• increase in the percentage of MEFs showing signs of replication-induced DNA damage after tamoxifen treatment

decreased fibroblast proliferation ( J:198698 )

• tamoxifen treatment impairs the long-term proliferative potential of MEFs

Genotype
MGI:5824831

cn9

• Allelic Composition: Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6

VEGF-C-and galectin-8-induced lymphangiogenesis is diminished in Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn Tg(CAG-cre/Esr1*)5Amc/0 mice

immune system

abnormal lymphangiogenesis ( J:235778 )

• in corneal micropocket assays, corneas implanted with either VEGF-C or galectin-8 pellets in tamoxifen-treated mice exhibit significantly reduced lymphangiogenesis relative to similarly-implanted wild-type corneas, as quantified by the lymphatic vessel area on day 7 post-surgery

Genotype
MGI:7282305

cn10

• Allelic Composition: Avpr2^tm2.1Jwe/Y; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6

behavior/neurological

polydipsia ( J:324922 )

♂ • 7- to 8-week-old males treated with tamoxifen for 6 days show an increase in water intake

♂ • treatment with the selective EP4 receptor agonist ONO results in a 50% decrease in cumulative water consumption

renal/urinary system

decreased urine creatinine level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine creatinine concentration

decreased urine potassium level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine potassium concentration

decreased urine sodium level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine sodium concentration

♂ • however, serum sodium levels are normal

decreased urine osmolality ( J:324922 )

♂ • urine produced by tamoxifen-treated males has very low osmolality

♂ • urine osmolality is lower by about 25% even prior to tamoxifen treatment

♂ • treatment with 1-desamino-8-D-AVP, a selective AVPR2 agonist, is unable to increase urine osmolality in tamoxifen-treated mice

♂ • treatment with the selective EP4 receptor agonist ONO leads to dose-dependent increases in urine osmolality in tamoxifen-administered mice

decreased urine urea nitrogen level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine urea

hydronephrosis ( J:324922 )

♂ • kidneys show distention of the renal pelvis after tamoxifen treatment

♂ • ONO treatment completely prevents further expansion of renal pelvic space in tamoxifen-administered mice

decreased renal glomerular filtration rate ( J:324922 )

♂ • tamoxifen-treated males show an approximate 40% reduction of glomerular filtration rate

♂ • ONO treatment restores normal glomerular filtration rate in tamoxifen-administered mice

polyuria ( J:324922 )

♂ • 7- to 8-week-old males treated with tamoxifen for 6 days show an increase in urine production

♂ • treatment with the selective EP4 receptor agonist ONO leads to a reduction in urine output in tamoxifen-administered mice

homeostasis/metabolism

decreased urine creatinine level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine creatinine concentration

decreased urine potassium level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine potassium concentration

decreased urine sodium level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine sodium concentration

♂ • however, serum sodium levels are normal

decreased urine osmolality ( J:324922 )

♂ • urine produced by tamoxifen-treated males has very low osmolality

♂ • urine osmolality is lower by about 25% even prior to tamoxifen treatment

♂ • treatment with 1-desamino-8-D-AVP, a selective AVPR2 agonist, is unable to increase urine osmolality in tamoxifen-treated mice

♂ • treatment with the selective EP4 receptor agonist ONO leads to dose-dependent increases in urine osmolality in tamoxifen-administered mice

decreased urine urea nitrogen level ( J:324922 )

♂ • tamoxifen-treated males show a reduction in urine urea

growth/size/body

decreased body weight ( J:324922 )

♂ • tamoxifen-treated males weigh approximately 25% less than controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
X-linked nephrogenic diabetes insipidus		DOID:0081060	OMIM:304800	J:324922

Genotype
MGI:5538607

cn11

• Allelic Composition: Tbx3^tm3.1Moon/Tbx3^tm3.1Moon; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6

Atrioventricular block in tamoxifen treated Tbx3^tm3.1Moon/Tbx3^tm3.1Moon Tg(CAG-cre/Esr1*)5Amc/0 mice

cardiovascular system

abnormal sinus arrhythmia ( J:179977 )

• in tamoxifen-treated mice

atrioventricular block ( J:179977 )

• second degree in tamoxifen-treated mice

Genotype
MGI:6712827

cn12

• Allelic Composition: Seh1l^tm1Lzha/Seh1l^tm1Lzha; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

nervous system

dysmyelination ( J:276253 )

• tamoxifen-treated mice show a translucent optic nerve indicating a severe deficiency of myelin formation

Genotype
MGI:6449234

cn13

• Allelic Composition: Dicer1^tm1Bdh/Dicer1^tm1Bdh; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

muscle

impaired skeletal muscle regeneration ( J:292144 )

• lower mean of regenerating myofiber cross-sectional area of tibialis anterior (TA) muscle 14 days after intramuscular injection of cardiotoxin (CTX), after induction of knockout with tamoxifen

• normal number of satellite cells and normal primary myoblast differentiation and viability after induction of knockout with tamoxifen

Genotype
MGI:5691394

cn14

• Allelic Composition: Hap1^tm2Xjl/Hap1^tm2Xjl; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

behavior/neurological

decreased coping response ( J:224698 )

• mice treated with tamoxifen at early postnatal times (P1), but not at late postnatal times or as adults, show increased immobility in the forced swim test and in the tail suspension test

• mice treated with tamoxifen at P21 do not exhibit impaired hippocampal neurogenesis under normal conditions, however after repeated restraint stress, these mice show an increase in immobility compared to non-stressed mutants and stressed controls

decreased locomotor activity ( J:224698 )

• mice treated with tamoxifen at an early age exhibit lower locomotor activity as adults

nervous system

impaired neuron differentiation ( J:224698 )

• mice treated with tamoxifen at P1 show impaired neuronal differentiation in the hippocampus as indicated by a lower ratio of NeuN+/BrdU+ cells than in controls and a higher ratio of GFAP+/BrdU+ cells among BrdU+ cells

abnormal neuron proliferation ( J:224698 )

• a decrease in proliferating cells is seen in the hippocampal dentate gyrus when mice are treated with tamoxifen at P1, but not when mice are treated with tamoxifen at P21

cellular

impaired neuron differentiation ( J:224698 )

• mice treated with tamoxifen at P1 show impaired neuronal differentiation in the hippocampus as indicated by a lower ratio of NeuN+/BrdU+ cells than in controls and a higher ratio of GFAP+/BrdU+ cells among BrdU+ cells

abnormal neuron proliferation ( J:224698 )

• a decrease in proliferating cells is seen in the hippocampal dentate gyrus when mice are treated with tamoxifen at P1, but not when mice are treated with tamoxifen at P21

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melancholic depression		DOID:1595	OMIM:608516	J:224698

Genotype
MGI:4353177

cn15

• Allelic Composition: Pax3^tm1.1Sjc/Pax3^tm1.1Sjc; Pax7^tm1.2Fan/Pax7^tm1.2Fan; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

muscle

muscle phenotype ( J:150962 )

N • following tamoxifen-treatment, muscle regeneration is normal as are the proliferative and myogenic properties of adult myoblasts

Genotype
MGI:4834592

cn16

• Allelic Composition: Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

growth/size/body

decreased body weight ( J:164406 )

• after cre induction by tamoxifen, mice show decrease in body relative to controls

cellular

abnormal lipid oxidation ( J:164406 )

• increased fat oxidation after loss of Tardbp results in fat loss in adipocytes

adipose tissue

decreased total body fat amount ( J:164406 )

• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice

• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass

abnormal brown fat cell morphology ( J:164406 )

• absence of fatty acid vacuoles in adipocytes in interscapular brown fat is detected

• adipocytes are present in brown fat, but lack of stored fat within adipocytes results in loss of fat content in animals after induction by tamoxifen

decreased mesenteric fat pad weight ( J:164406 )

• dramatic fat loss is observed

abnormal white adipose tissue morphology ( J:164406 )

abnormal white fat cell morphology ( J:164406 )

• reduction of fatty acid vacuoles in adipocytes in subcutaneous fat is detected

• adipocytes are present in white fat, but lack of stored fat within adipocytes results in loss of fat content in animals after induction by tamoxifen

homeostasis/metabolism

abnormal lipid oxidation ( J:164406 )

• increased fat oxidation after loss of Tardbp results in fat loss in adipocytes

Genotype
MGI:4834589

cn17

• Allelic Composition: Tardbp^tm1.1Pcw/Tardbp⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

growth/size/body

decreased body weight ( J:164406 )

• after cre induction by tamoxifen, mice show decrease in body weight relative to controls

adipose tissue

abnormal brown fat cell morphology ( J:164406 )

• absence of fatty acid vacuoles in adipocytes in interscapular brown fat is detected

abnormal white fat cell morphology ( J:164406 )

• reduction of fatty acid vacuoles in adipocytes in subcutaneous fat is detected

Genotype
MGI:3773016

cn18

• Allelic Composition: Sox4^tm1Vlf/Sox4^tm1Vlf; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

mortality/aging

prenatal lethality, complete penetrance ( J:130461 )

• when treated with tamoxifen, mice die between E13.5 and E14.5 likely due to regurgitation of blood into the heart

cardiovascular system

persistent truncus arteriosus ( J:130461 )

• when treated with tamoxifen

abnormal semilunar valve development ( J:130461 )

• endocardial cushions form at the level of the semilunar valve but functional flaps do not form when treated with tamoxifen

abnormal interventricular septum morphology ( J:130461 )

• at E13.5, mice exhibit incomplete septation of the ventricles when treated with tamoxifen

homeostasis/metabolism

edema ( J:130461 )

• at E13.5 when treated with tamoxifen

Genotype
MGI:5318110

cn19

• Allelic Composition: Cdk1^tm2.1Kald/Cdk1^tm2.1Kald; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

cellular

decreased cell proliferation ( J:182141 )

• in mouse embryonic fibroblasts treated with tamoxifen

early cellular replicative senescence ( J:182141 )

• in mouse embryonic fibroblasts treated with tamoxifen

abnormal DNA replication ( J:182141 )

• tamoxifen-treated mouse embryonic fibroblasts fail to exhibit DNA re-replication unlike control cells

• however, initial DNA replication is normal

neoplasm

decreased tumor growth/size ( J:182141 )

• following tamoxifen treatment of tumor cells induced by activated Ras

homeostasis/metabolism

abnormal DNA replication ( J:182141 )

• tamoxifen-treated mouse embryonic fibroblasts fail to exhibit DNA re-replication unlike control cells

• however, initial DNA replication is normal

Genotype
MGI:6194636

cn20

• Allelic Composition: Celf4^tm1.1Frk/Celf4^tm1.1Frk; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6J

behavior/neurological

convulsive seizures ( J:181678 )

• tamoxifen-induced deletion at 7 weeks of age is sufficient to cause a lowered threshold for handling-associated convulsive seizures

abnormal spike wave discharge ( J:181678 )

• tamoxifen-induced cre excision of Celf4 must occur by 1 day of age in order to develop a high incidence of spike wave discharge, and induced deletion at 5 to 7 days of age or later fails to result in increased absence seizures

nervous system

convulsive seizures ( J:181678 )

• tamoxifen-induced deletion at 7 weeks of age is sufficient to cause a lowered threshold for handling-associated convulsive seizures

abnormal spike wave discharge ( J:181678 )

• tamoxifen-induced cre excision of Celf4 must occur by 1 day of age in order to develop a high incidence of spike wave discharge, and induced deletion at 5 to 7 days of age or later fails to result in increased absence seizures

Genotype
MGI:5704117

cn21

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0; Ube3a^tm1Yelg/Ube3a⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPasCrl * C57BL/6J

behavior/neurological

abnormal emotion/affect behavior ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in marble burying, indicating no rescue of this phenotype when gene expression is re-established at those times

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams does not rescue the deficits in marble burying

abnormal depression-related behavior ( J:222400 )

• mice treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in the forced swim test, indicating no rescue of this phenotype

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams does not rescue the deficits in the forced swim test

impaired coordination ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 14 weeks (adults) do not show any rescue of motor coordination deficit at 28 weeks of age

• however, mice with a maternally inherited allele treated with tamoxifen at 6 weeks (adolescents) show partial rescue of motor coordination deficit at 22 weeks of age and mice treated with tamoxifen at 3 weeks (juveniles) show full rescue of motor coordination deficit at 16 weeks of age

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams rescues fully the motor coordination deficit

decreased locomotor activity ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in the open field explorations, indicating no rescue of this phenotype

• however, tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams results in improved performance in the open field

abnormal nest building behavior ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in nest building, indicating no rescue of this phenotype

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams does not rescue the deficits in nest building

audiogenic seizures ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3 weeks of age show increased audiogenic seizure threshold, indicating no rescue of this phenotype

nervous system

audiogenic seizures ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3 weeks of age show increased audiogenic seizure threshold, indicating no rescue of this phenotype

abnormal long-term potentiation ( J:222400 )

• mice with a maternally inherited allele not treated with tamoxifen exhibit abnormal Schaffer collateral-CA1 long term potentiation indicating a hippocampal plasticity deficit

• mice with a maternally inherited allele show full recovery of hippocampal LTP when treated with tamoxifen at 3 and 14 weeks of age

Genotype
MGI:4453346

cn22

• Allelic Composition: Lhx2^tm1Monu/Lhx2^tm1Dra; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA

integument

abnormal hair growth ( J:159209 )

• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair

abnormal hair cycle anagen phase ( J:159209 )

• unable to develop beyond Sub-stage III and assemble a normal hair shaft

Genotype
MGI:4453348

cn23

• Allelic Composition: Lhx2^tm1Monu/Lhx2^tm1Monu; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA

integument

abnormal hair growth ( J:159209 )

• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair

abnormal hair cycle anagen phase ( J:159209 )

• unable to develop beyond Sub-stage III and assemble a normal hair shaft

Genotype
MGI:3833891

cn24

• Allelic Composition: Supv3l1^tm2.1Jkl/Supv3l1^tm2.2Jkl; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N

Thymic atrophy in Supv3l1^tm2.1Jkl/Supv3l1^tm2.2Jkl Tg(CAG-cre/Esr1*)5Amc/0 mice

mortality/aging

premature death ( J:144991 )

• mice die by 15 weeks of age

• tamoxifen-treated mice die by 6 weeks of age

immune system

increased macrophage derived foam cell number ( J:144991 )

• in the lungs in tamoxifen-treated mice

thymus atrophy ( J:144991 )

• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice

thymus hypoplasia ( J:144991 )

• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

abnormal T cell differentiation ( J:144991 )

• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele

decreased double-negative T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased double-positive T cell number ( J:144991 )

• more than 10-fold in tamoxifen-treated mice

decreased CD4-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased CD8-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

lung inflammation ( J:144991 )

• chronic and acute in untreated and tamoxifen-treated mice

growth/size/body

decreased body weight ( J:144991 )

• in tamoxifen-treated mice

cachexia ( J:144991 )

adipose tissue

decreased subcutaneous adipose tissue amount ( J:144991 )

• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice

respiratory system

lung inflammation ( J:144991 )

• chronic and acute in untreated and tamoxifen-treated mice

abnormal lung interstitium morphology ( J:144991 )

• thickened in in tamoxifen-treated mice and untreated mice

muscle

decreased skeletal muscle mass ( J:144991 )

• mice exhibit sarcopenia atrophy that develops more rapidly in tamoxifen treated mice

dystrophic muscle ( J:144991 )

skeleton

kyphosis ( J:144991 )

• mice exhibit kyphosis that develops more rapidly in tamoxifen treated mice

endocrine/exocrine glands

thymus atrophy ( J:144991 )

• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice

thymus hypoplasia ( J:144991 )

• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

decreased sebaceous gland number ( J:144991 )

• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice

cardiovascular system

dilated vasculature ( J:144991 )

• tamoxifen-treated mice exhibit focal vascular ectasia in the skin unlike in untreated mice

• mice treated topically with tamoxifen exhibit dilated vasculature at the site of application

behavior/neurological

abnormal locomotor behavior ( J:144991 )

• locomotor functions fail in moribund mice

digestive/alimentary system

abnormal duodenum morphology ( J:144991 )

• tamoxifen-treated mice exhibit an increase in apoptosis compared to untreated mice

hematopoietic system

increased macrophage derived foam cell number ( J:144991 )

• in the lungs in tamoxifen-treated mice

thymus atrophy ( J:144991 )

• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice

thymus hypoplasia ( J:144991 )

• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

abnormal T cell differentiation ( J:144991 )

• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele

decreased double-negative T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased double-positive T cell number ( J:144991 )

• more than 10-fold in tamoxifen-treated mice

decreased CD4-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased CD8-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

cellular

increased macrophage derived foam cell number ( J:144991 )

• in the lungs in tamoxifen-treated mice

integument

integument phenotype ( J:144991 )

N • unlike in Supv3l1^tm2Jkl/Supv3l1^tm2Jkl floxed Tg(Mx1-cre)1Cgn mice, tamoxifen-treated mice exhibit normal hair growth

decreased subcutaneous adipose tissue amount ( J:144991 )

• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice

decreased sebaceous gland number ( J:144991 )

• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice

abnormal skin morphology ( J:144991 )

• tamoxifen treated mice exhibit focal vascular ectasia, reduced adipose tissue, and atrophic muscle layer in the skin unlike in untreated mice

abnormal dermal layer morphology ( J:144991 )

• apoptosis rates in the basal layer are increased in tamoxifen-treated mice compared to in untreated mice

hyperkeratosis ( J:144991 )

• mild in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen

parakeratosis ( J:144991 )

• at the site of tamoxifen application when applied directly to the skin

abnormal epidermis stratum granulosum morphology ( J:144991 )

• hypergranulosis develops in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen

acanthosis ( J:144991 )

• in tamoxifen-treated mice

thick epidermis ( J:144991 )

• in tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin

reddish skin ( J:144991 )

• at the site of tamoxifen application when applied directly to the skin

scaly skin ( J:144991 )

• on the skin and tails of tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin

Genotype
MGI:4361221

cn25

• Allelic Composition: St14^tm2Bug/St14^tm3Bug; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * CBA

mortality/aging

premature death ( J:153070 )

• mice are moribund within 9 to 10 days of tamoxifen treatment unlike similarly treated control mice

digestive/alimentary system

abnormal enterocyte morphology ( J:153070 )

• tamoxifen-treated mice exhibit disruption of tight junctions unlike similarly treated wild-type mice

abnormal large intestine morphology ( J:153070 )

• tamoxifen-treated mice exhibit dissolution of tissue architecture and pronounced edema of crypts and submucosa in the large intestine unlike in similarly treated control mice

abnormal large intestine crypts of Lieberkuhn morphology ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts unlike in similarly treated control mice

intestinal edema ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts and submucosa unlike in similarly treated control mice

absent digestive secretion ( J:153070 )

• in tamoxifen-treated mice

abnormal enterocyte physiology ( J:153070 )

• tamoxifen-treated mice exhibit a loss of intestinal barrier and increased intestinal permeability unlike similarly treated control mice

• tamoxifen-treated mice exhibit a 1.5-fold increase in epithelial cell transit through colonic crypts compared with similarly treated control mice

• tamoxifen-treated mice exhibit an increase in intestinal cell turnover compared with similarly treated control mice

craniofacial

abnormal facial morphology ( J:153070 )

• tamoxifen-treated mice exhibit scaling and inflammation of the orofacial surfaces unlike similarly treated control mice

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts unlike in similarly treated control mice

growth/size/body

abnormal facial morphology ( J:153070 )

• tamoxifen-treated mice exhibit scaling and inflammation of the orofacial surfaces unlike similarly treated control mice

weight loss ( J:153070 )

• in tamoxifen-treated mice despite normal food ingestion

cachexia ( J:153070 )

• in tamoxifen-treated mice

homeostasis/metabolism

intestinal edema ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts and submucosa unlike in similarly treated control mice

integument

alopecia ( J:153070 )

• in tamoxifen-treated mice

abnormal hair follicle morphology ( J:153070 )

• tamoxifen-treated mice exhibit follicular hyperplasia compared with similarly treated control mice

hyperkeratosis ( J:153070 )

• in tamoxifen-treated mice

scaly skin ( J:153070 )

• tamoxifen-treated mice exhibit retention and hyperproliferative ichthyosis unlike similarly treated control mice

skin fibrosis ( J:153070 )

• tamoxifen-treated mice exhibit dermal fibrosis unlike similarly treated control mice

Genotype
MGI:3833890

cn26

• Allelic Composition: Supv3l1^tm2Jkl/Supv3l1^tm2Jkl; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

Kyphosis and scaling on feet develop in Supv3l1^tm2Jkl/Supv3l1^tm2Jkl Tg(CAG-cre/Esr1*)5Amc/0 mice following tamoxifen treatment

mortality/aging

premature death ( J:144991 )

• mice die by 15 weeks of age

• tamoxifen-treated mice die by 6 weeks of age

immune system

increased macrophage derived foam cell number ( J:144991 )

• in the lungs in tamoxifen-treated mice

thymus atrophy ( J:144991 )

• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice

thymus hypoplasia ( J:144991 )

• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

abnormal T cell differentiation ( J:144991 )

• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele

decreased double-negative T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased double-positive T cell number ( J:144991 )

• more than 10-fold in tamoxifen-treated mice

decreased CD4-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased CD8-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

lung inflammation ( J:144991 )

• chronic and acute in untreated and tamoxifen-treated mice

growth/size/body

decreased body weight ( J:144991 )

• in tamoxifen-treated mice

cachexia ( J:144991 )

adipose tissue

decreased subcutaneous adipose tissue amount ( J:144991 )

• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice

respiratory system

lung inflammation ( J:144991 )

• chronic and acute in untreated and tamoxifen-treated mice

abnormal lung interstitium morphology ( J:144991 )

• thickened in in tamoxifen-treated mice and untreated mice

muscle

decreased skeletal muscle mass ( J:144991 )

• mice exhibit sarcopenia atrophy that develops more rapidly in tamoxifen treated mice

dystrophic muscle ( J:144991 )

skeleton

kyphosis ( J:144991 )

• mice exhibit kyphosis that develops more rapidly in tamoxifen treated mice

endocrine/exocrine glands

thymus atrophy ( J:144991 )

• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice

thymus hypoplasia ( J:144991 )

• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

decreased sebaceous gland number ( J:144991 )

• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice

cardiovascular system

dilated vasculature ( J:144991 )

• tamoxifen-treated mice exhibit focal vascular ectasia in the skin unlike in untreated mice

• mice treated topically with tamoxifen exhibit dilated vasculature at the site of application

behavior/neurological

abnormal locomotor behavior ( J:144991 )

• locomotor functions fail in moribund mice

digestive/alimentary system

abnormal duodenum morphology ( J:144991 )

• tamoxifen-treated mice exhibit an increase in apoptosis compared to untreated mice

hematopoietic system

increased macrophage derived foam cell number ( J:144991 )

• in the lungs in tamoxifen-treated mice

thymus atrophy ( J:144991 )

• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice

thymus hypoplasia ( J:144991 )

• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

abnormal T cell differentiation ( J:144991 )

• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele

decreased double-negative T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased double-positive T cell number ( J:144991 )

• more than 10-fold in tamoxifen-treated mice

decreased CD4-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

decreased CD8-positive, alpha-beta T cell number ( J:144991 )

• in tamoxifen-treated mice

cellular

increased macrophage derived foam cell number ( J:144991 )

• in the lungs in tamoxifen-treated mice

integument

integument phenotype ( J:144991 )

N • unlike in Supv3l1^tm2Jkl/Supv3l1^tm2Jkl floxed Tg(Mx1-cre)1Cgn mice, tamoxifen-treated mice exhibit normal hair growth

decreased subcutaneous adipose tissue amount ( J:144991 )

• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice

decreased sebaceous gland number ( J:144991 )

• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice

abnormal skin morphology ( J:144991 )

• tamoxifen treated mice exhibit focal vascular ectasia, reduced adipose tissue, and atrophic muscle layer in the skin unlike in untreated mice

abnormal dermal layer morphology ( J:144991 )

• apoptosis rates in the basal layer are increased in tamoxifen-treated mice compared to in untreated mice

hyperkeratosis ( J:144991 )

• mild in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen

parakeratosis ( J:144991 )

• at the site of tamoxifen application when applied directly to the skin

abnormal epidermis stratum granulosum morphology ( J:144991 )

• hypergranulosis develops in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen

acanthosis ( J:144991 )

• in tamoxifen-treated mice

thick epidermis ( J:144991 )

• in tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin

reddish skin ( J:144991 )

• at the site of tamoxifen application when applied directly to the skin

scaly skin ( J:144991 )

• on the skin and tails of tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin

Genotype
MGI:5466536

cn27

• Allelic Composition: Mcat^tm1.1Ssmi/Mcat^tm1.1Ssmi; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA

Hair loss and dry skin in tamoxifen treated Mcat^tm1.1Ssmi/Mcat^tm1.1Ssmi Tg(CAG-cre/Esr1*)5Amc/0 mice

mortality/aging

premature death ( J:192213 )

• severely affected tamoxifen-treated mice develop pruritus that leads to self-inflicted scratch wounds and necessitates euthanasia

• tamoxifen-treated mice that do not require euthanasia exhibit mean survival time of 293 days post-induction

hematopoietic system

enlarged spleen ( J:192213 )

• in tamoxifen-treated mice

abnormal myelopoiesis ( J:192213 )

• myeloid hematopoiesis in the bone marrow of some tamoxifen-treated mice

extramedullary hematopoiesis ( J:192213 )

• in some tamoxifen-treated mice

anemia ( J:192213 )

• in some tamoxifen-treated mice

decreased erythrocyte cell number ( J:192213 )

• in some tamoxifen-treated mice

decreased hematocrit ( J:192213 )

• in some tamoxifen-treated mice

decreased hemoglobin content ( J:192213 )

• in some tamoxifen-treated mice

increased mean corpuscular volume ( J:192213 )

• in some tamoxifen-treated mice

increased red blood cell distribution width ( J:192213 )

• in some tamoxifen-treated mice

decreased leukocyte cell number ( J:192213 )

♀ • minor in some female tamoxifen-treated mice

decreased lymphocyte cell number ( J:192213 )

♀ • minor in some female tamoxifen-treated mice

abnormal reticulocyte morphology ( J:192213 )

• tamoxifen-treated mice that develop anemia exhibit increased number and size of reticulocyte compared with control mice

reticulocytosis ( J:192213 )

• in some tamoxifen-treated mice

abnormal erythrocyte physiology ( J:192213 )

• anemic tamoxifen-treated mice exhibit reduced red blood cell lifespan compared with control mice

behavior/neurological

behavior/neurological phenotype ( J:192213 )

N • tamoxifen-treated mice exhibit normal balance and motor coordination

decreased exploration in new environment ( J:192213 )

• in tamoxifen-treated mice

abnormal eating behavior ( J:192213 )

• in tamoxifen-treated mice

excessive scratching ( J:192213 )

• severely affected tamoxifen-treated mice develop pruritus that leads to self-inflicted scratch wounds and necessitates euthanasia

tremors ( J:192213 )

• shivering in tamoxifen-treated mice

decreased grip strength ( J:192213 )

• in tamoxifen-treated mice

abnormal gait ( J:192213 )

• tamoxifen-treated mice walk with splayed hind limbs and drag their posterior unlike control mice

decreased vertical activity ( J:192213 )

• in tamoxifen-treated mice

decreased locomotor activity ( J:192213 )

• reduced exploration and overall activity in an open field test in tamoxifen-treated mice

impaired exercise endurance ( J:192213 )

• tamoxifen-treated mice on a constantly spinning rotarod exhibit reduced endurance compared with control mice

homeostasis/metabolism

impaired exercise endurance ( J:192213 )

• tamoxifen-treated mice on a constantly spinning rotarod exhibit reduced endurance compared with control mice

increased circulating glucose level ( J:192213 )

• in tamoxifen-treated mice

increased circulating lactate level ( J:192213 )

• tamoxifen-treated mice exhibit elevated plasma lactate compared with control mice

abnormal circulating alanine transaminase level ( J:192213 )

• decreased in tamoxifen-treated mice

decreased body temperature ( J:192213 )

• in tamoxifen-treated mice

increased skeletal muscle glycogen level ( J:192213 )

• in tamoxifen-treated mice

increased circulating chloride level ( J:192213 )

• in tamoxifen-treated mice

abnormal lipid homeostasis ( J:192213 )

• tamoxifen-treated mice exhibit compromised fatty acid synthesis due to reduced availability of precursors for lipoylation of key mitochondrial enzymes compared with control mice

increased circulating ketone body level ( J:192213 )

• tamoxifen-treated mice exhibit elevated plasma ketone bodies compared with control mice

integument

decreased subcutaneous adipose tissue amount ( J:192213 )

• in tamoxifen-treated mice

abnormal coat appearance ( J:192213 )

• beginning 3 to 4 months after tamoxifen-treatment, coats have lost their normal luster compared with controls

alopecia ( J:192213 )

• beginning 3 to 4 months after tamoxifen-treatment eventually resulting in severe baldness

hyperkeratosis ( J:192213 )

• in tamoxifen-treated mice

dry skin ( J:192213 )

• in tamoxifen-treated mice

increased pruritus ( J:192213 )

• in severely affected tamoxifen-treated mice that leads to self-inflicted scratch wounds, necessitating euthanasia

digestive/alimentary system

digestive/alimentary phenotype ( J:192213 )

N • tamoxifen-treated mice exhibit normal digestion

rectal hemorrhage ( J:192213 )

• from prolapsed rectum in anemic tamoxifen-treated mice

• however, no blood is observed in the feces

rectal prolapse ( J:192213 )

• in 9 of 10 anemic tamoxifen-treated mice

cardiovascular system

rectal hemorrhage ( J:192213 )

• from prolapsed rectum in anemic tamoxifen-treated mice

• however, no blood is observed in the feces

growth/size/body

decreased body weight ( J:192213 )

• tamoxifen-treated mice fail to gain weight

weight loss ( J:192213 )

• after 6 months in tamoxifen-treated mice

enlarged spleen ( J:192213 )

• in tamoxifen-treated mice

immune system

abnormal myelopoiesis ( J:192213 )

• myeloid hematopoiesis in the bone marrow of some tamoxifen-treated mice

decreased leukocyte cell number ( J:192213 )

♀ • minor in some female tamoxifen-treated mice

decreased lymphocyte cell number ( J:192213 )

♀ • minor in some female tamoxifen-treated mice

abnormal immune system organ morphology ( J:192213 )

• lymphoid atrophy in some tamoxifen-treated mice

enlarged spleen ( J:192213 )

• in tamoxifen-treated mice

adipose tissue

decreased subcutaneous adipose tissue amount ( J:192213 )

• in tamoxifen-treated mice

decreased white adipose tissue amount ( J:192213 )

• in tamoxifen-treated mice

cellular

abnormal cellular respiration ( J:192213 )

• tamoxifen-treated mice exhibit compromised mitochondrial respiration due to defects in protein lipoylation and respiratory complexes compared with wild-type mice

abnormal mitochondrial physiology ( J:192213 )

• tamoxifen-treated mice exhibit compromised mitochondrial respiration due to defects in protein lipoylation and respiratory complexes compared with wild-type mice

muscle

increased skeletal muscle glycogen level ( J:192213 )

• in tamoxifen-treated mice

abnormal muscle physiology ( J:192213 )

• increased glycogen and lactate levels in skeletal muscle of tamoxifen-treated mice

skeleton

kyphosis ( J:192213 )

• in tamoxifen-treated mice

Genotype
MGI:5524264

cn28

• Allelic Composition: Nrg1^tm3Cbm/Nrg1^tm3Cbm; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

muscle

abnormal muscle spindle morphology ( J:199150 )

• small diameter with degeneration of the outer capsule in tamoxifen-treated mice

• however, innervation is normal

decreased muscle spindle number ( J:199150 )

• in tamoxifen-treated mice

behavior/neurological

impaired coordination ( J:199150 )

• tamoxifen-treated mice hang on to an inverted grid 3 to 4 times less than controls mice

• strongly impaired in a beam-walking test

nervous system

abnormal muscle spindle morphology ( J:199150 )

• small diameter with degeneration of the outer capsule in tamoxifen-treated mice

• however, innervation is normal

decreased muscle spindle number ( J:199150 )

• in tamoxifen-treated mice

Genotype
MGI:3832684

cn29

• Allelic Composition: Mecp2^tm2Bird/Y; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

premature death ( J:118365 )

♂ • 9 of 17 mice treated with tamoxifen at 3 to 4 weeks of age die soon after treatment

♂ • however, tamoxifen-tocixity is not responsible for observed deaths, 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age have a normal life span, and mice treated with tamoxifen from week 12 to 17 exhibit normal lethality

behavior/neurological

behavior/neurological phenotype ( J:118365 )

♂N • the surviving 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age exhibit normal behavior/neurological phenotypes

abnormal behavior ( J:118365 )

♂ • at 12 weeks mice display low stance, inertia, tremor, arrhythmic breathing, splayed himdlimb and moderate hindlimb clasping

♂ • during the last 4 weeks of life, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition)

♂ • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms

limb grasping ( J:118365 )

♂ • at 12 weeks, mice display moderate hindlimb clasping

♂ • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms

tremors ( J:118365 )

♂ • at 12 weeks

♂ • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms

respiratory system

abnormal breathing pattern ( J:118365 )

♂ • at 12 weeks

♂ • mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms

Genotype
MGI:4830343

cn30

• Allelic Composition: Reck^tm1Ito/Reck^tm1.1Noda; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:163845 )

• mice treated with tamoxifen at E11 die after E15.5

cardiovascular system

abnormal blood vessel morphology ( J:163845 )

• at E15.5, blood vessels in tamoxifen-treated mice are large and irregularly shaped compared to in wild-type mice

abnormal brain vasculature morphology ( J:163845 )

• brain vasculature in tamoxifen-treated mice is disorganized and interrupted by large spaces and cavities unlike in wild-type mice

abnormal liver vasculature morphology ( J:163845 )

• the blood vessels in the livers of tamoxifen-treated mice exhibit larger luminal spaces than in wild-type mice

abnormal developmental vascular remodeling ( J:163845 )

• at E15.5, blood vessels in tamoxifen-treated mice are large and irregularly shaped compared to in wild-type mice

• brain vasculature in tamoxifen-treated mice is disorganized and interrupted by large spaces and cavities unlike in wild-type mice

• the blood vessels in the livers of tamoxifen-treated mice exhibit larger luminal spaces than in wild-type mice

dilated vasculature ( J:163845 )

• in tamoxifen-treated mice

hemorrhage ( J:163845 )

• at E15.5 in tamoxifen-treated mice

growth/size/body

decreased fetal size ( J:163845 )

• at E15.5 in tamoxifen-treated mice

liver/biliary system

abnormal liver vasculature morphology ( J:163845 )

• the blood vessels in the livers of tamoxifen-treated mice exhibit larger luminal spaces than in wild-type mice

nervous system

abnormal brain vasculature morphology ( J:163845 )

• brain vasculature in tamoxifen-treated mice is disorganized and interrupted by large spaces and cavities unlike in wild-type mice

integument

pallor ( J:163845 )

• at E15.5 in tamoxifen-treated mice

Genotype
MGI:3712287

cn31

• Allelic Composition: Mecp2^tm2Bird/Mecp2⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

behavior/neurological

abnormal behavior ( J:118365 )

♀ • at 4 to 12 months of age, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition)

♀ • however, tamoxifen treatment after the onset of symptoms reverses symptom progression

limb grasping ( J:118365 )

♀ • at 4 to 12 months of age

♀ • however, tamoxifen treatment after the onset of symptoms reverses symptom progression

tremors ( J:118365 )

♀ • at 4 to 12 months of age

♀ • however, tamoxifen treatment after the onset of symptoms reverses symptom progression

nervous system

reduced long-term potentiation ( J:118365 )

♀ • mice develop a reduction in long term potentiation

♀ • however, treatment with tamoxifen returns long term potentiation to normal levels

respiratory system

abnormal breathing pattern ( J:118365 )

♀ • at 4 to 12 months of age

♀ • however, tamoxifen treatment after the onset of symptoms reverses symptom progression

growth/size/body

obese ( J:118365 )

♀ • mice exhibit excess weight gain

♀ • however, tamoxifen treatment after the onset of symptoms reverses weight gain

Genotype
MGI:5287435

cn32

• Allelic Composition: Ppp2r1a^tm1.1Wltr/Ppp2r1a^tm1.2Wltr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * C57BL/6 * CBA * FVB/NCrl

mortality/aging

premature death ( J:175748 )

• mice die 6 days after tamoxifen treatment

behavior/neurological

ataxia ( J:175748 )

• tamoxifen-treated mice exhibit difficulty walking compared with control mice

hunched posture ( J:175748 )

• in tamoxifen-treated mice

growth/size/body

weight loss ( J:175748 )

• in tamoxifen-treated mice beyond the initial drop associated with tamoxifen treatment alone

Genotype
MGI:5903288

cn33

• Allelic Composition: Dohh^tm1.1Sbal/Dohh^tm1.1Sbal; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ

mortality/aging

premature death ( J:236582 )

• 1 to 5 weeks after tamoxifen treatment

growth/size/body

decreased body weight ( J:236582 )

• in tamoxifen-treated mice

cachexia ( J:236582 )

• in tamoxifen-treated mice due to wasting syndrome

renal/urinary system

renal tubular necrosis ( J:236582 )

• in one tamoxifen-treated mouse

increased kidney iron level ( J:236582 )

• enhanced ferrous iron incorporation in the kidney of 2 of 4 tamoxifen-treated mice

liver/biliary system

hepatic necrosis ( J:236582 )

• in two tamoxifen-treated mice

focal hepatic necrosis ( J:236582 )

• diffuse in one tamoxifen-treated mouse

homeostasis/metabolism

increased kidney iron level ( J:236582 )

• enhanced ferrous iron incorporation in the kidney of 2 of 4 tamoxifen-treated mice

hematopoietic system

hematopoietic system phenotype ( J:236582 )

N • tamoxifen-treated mice exhibit normal bone marrow cellularity

cellular

hepatic necrosis ( J:236582 )

• in two tamoxifen-treated mice

focal hepatic necrosis ( J:236582 )

• diffuse in one tamoxifen-treated mouse

renal tubular necrosis ( J:236582 )

• in one tamoxifen-treated mouse

Genotype
MGI:3767640

cn34

• Allelic Composition: Bub1^tm1Ssta/Bub1^tm1.1Ssta; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

cellular

abnormal cell cycle ( J:128455 )

• sister chromatid cohesion is defective in tamoxifen-treated mouse embryonic fibroblasts

abnormal mitotic spindle assembly checkpoint ( J:128455 )

• the spindle assembly checkpoint is defective in tamoxifen-treated mouse embryonic fibroblasts

decreased cell proliferation ( J:128455 )

• unlike untreated cells, tamoxifen-treated mouse embryonic fibroblasts stop proliferating in culture

Genotype
MGI:4360189

cn35

• Allelic Composition: Inpp5e^tm1.1Ssch/Inpp5e^tm1.2Ssch; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

growth/size/body

increased body weight ( J:152712 )

• mice display increased body weight after tamoxifen treatment

kidney cortex cyst ( J:152712 )

• glomerular cysts are seen in 6 month old tamoxifen treated mice

renal/urinary system

kidney cortex cyst ( J:152712 )

• glomerular cysts are seen in 6 month old tamoxifen treated mice

vision/eye

abnormal retina photoreceptor layer morphology ( J:152712 )

• after tamoxifen treatment the retinal photoreceptor layer is completely absent

Genotype
MGI:5305034

cn36

• Allelic Composition: Dscam^tm1Pfu/Dscam^tm1Pfu; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

vision/eye

abnormal amacrine cell morphology ( J:179393 )

• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped

increased amacrine cell number ( J:179393 )

• following tamoxifen treatment at P0

abnormal retina ganglion cell morphology ( J:179393 )

• following tamoxifen treatment at P0 2?3 fasciculated groups of melanopsin positive retinal ganglion cells are seen in each retina

nervous system

abnormal axon fasciculation ( J:179393 )

• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped

• following tamoxifen treatment at P0, 2?3 fasciculated groups of retinal ganglion cells are seen in each retina

• however with tamoxifen treatment at P0 or in adults no fasiculation of amacrine cell neurites is seen

abnormal amacrine cell morphology ( J:179393 )

• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped

increased amacrine cell number ( J:179393 )

• following tamoxifen treatment at P0

abnormal retina ganglion cell morphology ( J:179393 )

• following tamoxifen treatment at P0 2?3 fasciculated groups of melanopsin positive retinal ganglion cells are seen in each retina

cellular

abnormal axon fasciculation ( J:179393 )

• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped

• following tamoxifen treatment at P0, 2?3 fasciculated groups of retinal ganglion cells are seen in each retina

• however with tamoxifen treatment at P0 or in adults no fasiculation of amacrine cell neurites is seen

Genotype
MGI:3767641

cn37

• Allelic Composition: Bub1^tm1Ssta/Bub1^tm1Ssta; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

reproductive system

small seminiferous tubules ( J:128455 )

♂ • after mice are treated with tamoxifen for 8 weeks, tubules exhibit decreased celullarity and diameter

♂ • tubules containing only Sertoli cells are often observed

decreased testis weight ( J:128455 )

♂ • after mice are treated with tamoxifen for 8 weeks, testis weight is decreased by 50% of wild-type

abnormal spermatogenesis ( J:128455 )

♂ • after mice are treated with tamoxifen for 8 weeks, mitotic clusters of cells observed are often stuck in anaphase and abnormal chromosome content is observed

oligozoospermia ( J:128455 )

♂ • after mice are treated with tamoxifen for 8 weeks, no male germ cells are observed

♂ • after mice are treated with tamoxifen for 8 weeks, sperm production is reduced by 80% of wild-type

male infertility ( J:128455 )

♂ • after treated with tamoxifen for 4 weeks, adult males become infertile

cellular

oligozoospermia ( J:128455 )

♂ • after mice are treated with tamoxifen for 8 weeks, no male germ cells are observed

♂ • after mice are treated with tamoxifen for 8 weeks, sperm production is reduced by 80% of wild-type

decreased mitotic index ( J:128455 )

• after mice are treated with tamoxifen for 8 weeks, male testes have reduced mitotic index

growth/size/body

decreased fetal size ( J:128455 )

• when mice are treated with tamoxifen beginning at E10.5, by E18.5 mice resemble E10.5 to E11.5 mice

fetal growth retardation ( J:128455 )

• when mice are treated with tamoxifen beginning at E10.5, by E18.5 mice resemble E10.5 to E11.5 mice

endocrine/exocrine glands

small seminiferous tubules ( J:128455 )

♂ • after mice are treated with tamoxifen for 8 weeks, tubules exhibit decreased celullarity and diameter

♂ • tubules containing only Sertoli cells are often observed

decreased testis weight ( J:128455 )

♂ • after mice are treated with tamoxifen for 8 weeks, testis weight is decreased by 50% of wild-type

Genotype
MGI:4438398

cn38

• Allelic Composition: Edn2^tm1.1Nat/Edn2^tm1.1Nat; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

Impaired lung morphology in Edn2^tm1Ywa/Edn2^tm1Ywa mice and tamoxifen-treated Edn2^tm1.1Nat/Edn2^tm1.1Nat Tg(CAG-cre/Esr1*)5Amc/0 mice

mortality/aging

premature death ( J:201436 )

• in mice treated with tamoxifen at P0

• however, adult mice treated with tamoxifen exhibit normal survival

postnatal lethality, incomplete penetrance ( J:201436 )

• in mice treated with tamoxifen at P0

homeostasis/metabolism

impaired adaptive thermogenesis ( J:201436 )

• decreased body temperature in response to cold exposure in mice treated with tamoxifen

acidemia ( J:201436 )

• blood pH is more acidic in tamoxifen-treated mice

increased circulating bicarbonate level ( J:201436 )

• in tamoxifen-treated mice

decreased circulating glucose level ( J:201436 )

• in mice treated with tamoxifen at P0 or 6 weeks of age

decreased body temperature ( J:201436 )

• in mice treated with tamoxifen at P0 or 6 weeks of age

hypercapnia ( J:201436 )

• in tamoxifen-treated mice

acidosis ( J:201436 )

• blood pH is more acidic in tamoxifen-treated mice

growth/size/body

decreased body weight ( J:201436 )

• in mice treated with tamoxifen at P0 or 6 weeks of age

postnatal growth retardation ( J:201436 )

• in mice treated with tamoxifen at P0 or 6 weeks of age

respiratory system

abnormal pulmonary alveolar sac morphology ( J:201436 )

• tamoxifen-treated mice exhibit enlarged air spaces with simplification of the alveolar structure

abnormal pulmonary alveolus morphology ( J:201436 )

• simplified structure in tamoxifen-treated mice

adipose tissue

decreased total body fat amount ( J:201436 )

• after 10 weeks of tamoxifen-induced activation

Genotype
MGI:5438129

cn39

• Allelic Composition: Sdhd^tm1Jlob/Sdhd^tm2Jlob; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:186713 )

• in tamoxifen-treated mice

nervous system

nervous system phenotype ( J:186713 )

N • tamoxifen-treatment does not affect brain catecholaminergic neurons matured at birth

cardiovascular system

abnormal carotid body morphology ( J:186713 )

• tamoxifen-treated mice exhibit a trend towards degeneration of the carotid body

neoplasm

neoplasm ( J:186713 )

N • tamoxifen-treated mice do not develop tumors

Genotype
MGI:5431829

cn40

• Allelic Composition: Kcnq1ot1^tm2.1Ckan/Kcnq1ot1⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SD7

cellular

abnormal DNA methylation ( J:185569 )

• loss of methylation in the somatic differentially methylated regions following tamoxifen treatment at E8.5 when the Kcnq1ot1 allele is inherited paternally

abnormal imprinting ( J:185569 )

• loss of imprinting of ubiquitously imprinted genes following tamoxifen treatment at E8.5 when the Kcnq1ot1 allele is inherited paternally

• however, silencing of placental-specific imprinted genes is variably maintained

• no alteration of imprinting status when the Kcnq1ot1 allele is inherited maternally

Genotype
MGI:3838126

cn41

• Allelic Composition: Numa1^tm1.1Dwc/Numa1^tm1.1Dwc; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL

Spindle defects in primay Numa1^tm1.1Dwc/Numa1^tm1.1Dwc Tg(CAG-cre/Esr1*)5Amc/0 fibroblasts

cellular

cellular phenotype ( J:146214 )

N • despite spindle defects, bulk chromosome segregation is largely normal

abnormal mitotic spindle morphology ( J:146214 )

• tamoxifen-treated mouse embryonic fibroblasts (MEFs) exhibit detachment of microtubule-nucleating structures from the ends of the mitotic spindles unlike wild-type cells

• 50% of metaphase-like tamoxifen-treated MEFs have at least one centrosome that is not clearly associated with a spindle pole unlike in wild-type cells

• tension between sister kinetochores in pole-focused spindles in tamoxifen-treated MEFs exposed to MG132 is 33% less than in wild-type cells

• more like tamoxifen-treated MEFs exhibit pole defocusing and centrosome detachment than in wild-type cells

absent fibroblast proliferation ( J:146214 )

• tamoxifen-treated mouse embryonic fibroblasts (MEFs) fail to increase in number after release from growth arrest unlike wild-type cells

Genotype
MGI:7266814

cn42

• Allelic Composition: Htt^tm1Mem/Htt^tm6Mem; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * Swiss Webster

behavior/neurological

behavior/neurological phenotype ( J:260244 )

N • mice administered tamoxifen after P21 exhibit progressive neurological abnormalities; all abnormalities reported below are in mice treated with tamoxifen from P21-P26

limb grasping ( J:260244 )

• tamoxifen-treated mice exhibit clasping

impaired coordination ( J:260244 )

• mice administered tamoxifen from P21 to P26 exhibit abnormalities of motor coordination at 6 months of age

straub tail ( J:260244 )

• mice administered tamoxifen after P21 show Straub tail at one year of age

abnormal gait ( J:260244 )

• tamoxifen-treated mice exhibit gait disturbances at one year of age, including flattened pelvic elevation, abnormally wide hindlimb stance, and occasional hopping and stiffness

• gait abnormalities worsen over time such that 1-year-old mice lack the typical uniformity of step alternation and exhibit smaller gait strides

short stride length ( J:260244 )

• 1-year-old tamoxifen-treated mice exhibit smaller gait strides

hyperactivity ( J:260244 )

• mice administered tamoxifen from P21 to P26 exhibit a hyperkinetic phenotype at 6 months of age

environmentally induced seizures ( J:260244 )

• tamoxifen-treated mice exhibit handling induced seizures, characterized by alternating clonic movement of forelimbs, clonic and versive movements of the head, chewing movement and facial myoclonus, flagpole tail dodrsiflexion, followed by intermittent eye blinking, immobility, head nodding and clonic mouth jerks

growth/size/body

decreased body weight ( J:260244 )

• mice administered tamoxifen from P21 to P26 consistently show lower weight during adult life

muscle

muscular atrophy ( J:260244 )

• 16-month-old mice exhibit atrophy of hindlimb muscles when tamoxifen is administered after P21

nervous system

environmentally induced seizures ( J:260244 )

• tamoxifen-treated mice exhibit handling induced seizures, characterized by alternating clonic movement of forelimbs, clonic and versive movements of the head, chewing movement and facial myoclonus, flagpole tail dodrsiflexion, followed by intermittent eye blinking, immobility, head nodding and clonic mouth jerks

abnormal cerebral cortex morphology ( J:260244 )

• the number of degenerating neurons in the outer cortical layers of tamoxifen-treated mice, especially in layer III/IV is increased

abnormal primary motor cortex morphology ( J:260244 )

• layer VI thickness and numbers of neurons are reduced in the motor cortex of 12-month-old tamoxifen-treated mice

• the number of degenerating neurons in the deep layer motor cortex are increased in 12-month-old tamoxifen-treated mice

• the reduction in motor cortex layer VI is seen as early as 3 months of age, however the number of neurons in layer VI is comparable to wild-type at this age

abnormal cerebellum lobule morphology ( J:260244 )

• majority of tamoxifen-treated mice exhibit smaller cerebellar lobules

abnormal oligodendrocyte morphology ( J:260244 )

• P21 mice show fewer APC+ smooth- and ramified-type oligodendrocytes

• 3-month-old mice show a reduction of smooth- and ramified-type oligodendrocytes in layer VI of the motor cortex, with an increase of stellar-type oligodendrocytes

• however, overall number of APC+ oligodendrocytes is normal in 3-month-old tamoxifen-treated mice

• oligodendrocyte progenitors derived from primary embryonic neuronal stem cells display progressive maturation abnormalities, with impairments in the transition from proliferating progenitors to post-mitotic precursors and subsequent maturation and myelination

gliosis ( J:260244 )

• 83.3% of 12-month-old tamoxifen-treated mice exhibit striatal reactive gliosis, with exceedingly severe gliosis in the globus pallidum

astrocytosis ( J:260244 )

• reactive astrogliosis in superficial and cortical layers already at 3 months of age

abnormal nervous system development ( J:260244 )

• marker analysis indicates the presence of deficits in early neural lineage specification, migration, and regional organization, with impairments in the maturation of striatal compartmentalization

abnormal lateral ganglionic eminence morphology ( J:260244 )

• loss of the typical palisade appearance of pseudostratified neuroepithelium encompassing Mash1+ neuronal progenitors within the E15.5 lateral ganglionic eminence

ectopic neuron ( J:260244 )

• all fetuses (E14.5, E15.5, and E17.5) and early postnatal mice (P2, P10, and P21) exhibit analogous masses consisting of heterotopic evaginations of germinative zone-derived cells from the posterior ventromedial aspect of the lateral ganglionic eminence indicating subpallial ventricular heterotopias

neuronal cytoplasmic inclusions ( J:260244 )

• a number of non-degenerative cortical neurons of tamoxifen-treated mice, particularly those in layer III/IV, exhibit intracytoplasmic inclusions corresponding to concentric membrane-bound laminated inclusions of zebra bodies

neurodegeneration ( J:260244 )

• tamoxifen-treated mice develop progressive striatal neurodegenerative pathology and cortical deep layer degeneration

• 27.3% of 12-month-old tamoxifen-treated mice show degenerative changes in the posterior ventrolateral striatum and the endopiriform claustrum

axon degeneration ( J:260244 )

• motor cortex of tamoxifen-treated mice shows axons of larger caliber displaying Wallerian-like degenerative morphology

dysmyelination ( J:260244 )

• 12-month-old tamoxifen-treated mice exhibit hypomyelinated axons in cortical deep layers, as well as axons with myelin balloons and tuberovesicular structures

• myelination defects preferentially affect axons of larger caliber, with reduced periodicity of myelin lamellae in large axons

• similar myelin defects are seen on white matter tracts containing axonal bundles traveling across the striatum

skeleton

lordokyphosis ( J:260244 )

• 16-month-old mice exhibit lordokyphosis when tamoxifen is administered after P21

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:260244

Genotype
MGI:5795834

cn43

• Allelic Composition: Pnkp^tm1.1Pmc/Pnkp^tm1.1Pmc; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

cellular

increased brain apoptosis ( J:226703 )

• mice treated with tamoxifen at P10 (3 doses every 2 days) exhibit apoptosis in the dentate gyrus at P20

growth/size/body

decreased body size ( J:226703 )

• mice treated with tamoxifen at P7 exhibit a decreased body size at P13

• mice treated with tamoxifen at P10 (3 doses every 2 days) exhibit a modest effect on brain size at P20

nervous system

increased brain apoptosis ( J:226703 )

• mice treated with tamoxifen at P10 (3 doses every 2 days) exhibit apoptosis in the dentate gyrus at P20

decreased brain size ( J:226703 )

• mice treated with tamoxifen at P7 exhibit decreased brain size

• however, mice treated with tamoxifen at P21 (3 doses every 2 days) exhibit little overall effect on brain size or structure

abnormal cerebellar cortex morphology ( J:226703 )

• mice treated with tamoxifen at P7 exhibit a reduction in cortical size

decreased oligodendrocyte number ( J:226703 )

• mice treated with tamoxifen at P21 (3 doses every 2 days) exhibit a decrease in oligodendrocyte numbers in the dentate gyrus but not in the cortex at P33

decreased neuron number ( J:226703 )

• mice treated with tamoxifen at P21 show a reduction of mature neurons in the dentate gyrus, the hippocampal CA3 region and the cerebellum

abnormal myelination ( J:226703 )

• myelin-producing oligodendrocytes from mice treated with tamoxifen at P21 show a reduction in myelination

• mice treated with tamoxifen at P10 (3 doses every 2 days) exhibit a loss of myelination in the dentate gyrus at P20

• mice treated with tamoxifen at P14 (3 doses every 2 days) exhibit a loss of myelination of oligodendrocytes at P30

Genotype
MGI:5784520

cn44

• Allelic Composition: Gls^tm2.1Sray/Gls⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

behavior/neurological

impaired behavioral response to amphetamine ( J:230564 )

• attenuated locomotor response to amphetamine in tamoxifen-treated mice as compared to controls

• amphetamine-induced hyperlocomotion is blocked in open field test

abnormal locomotor activation ( J:230564 )

• decrease in fine movements, but not rearing, following administration of amphetamine in tamoxifen-treated mice as compared to controls

Genotype
MGI:4415303

cn45

• Allelic Composition: Ate1^tm1Avar/Ate1^tm2.1Avar; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

Small and lean phenotype of Ate1^tm1Avar/Ate1^tm2.1Avar Tg(CAG-cre/Esr1*)5Amc/0 mice

mortality/aging

premature death ( J:155421 )

• 15% (18 of 119 mice) die over 42 days after TM treatment

• 46% of mice younger than 30 days at the beginning of TM treatment die within 42 days after TM treatment

• 12% of mice die if they are older than 30 days (up to 56 days) at the beginning of TM treatment

growth/size/body

increased heart weight ( J:155421 )

• hearts are disproportionately large

slow postnatal weight gain ( J:155421 )

• decreased growth

• attaining only 70% of normal weight

• no decrease in their consumption of food

weight loss ( J:155421 )

• during the first 3 weeks after TM treatment, rapid loss of weight

decreased body length ( J:155421 )

• all the phenotypes below are induced by tamoxifen (TM) treatment

• 5% smaller average body length (p<0.08)

decreased susceptibility to diet-induced obesity ( J:155421 )

• resistant to high-fat diet induced obesity

increased kidney weight ( J:155421 )

• kidneys are disproportionately large

behavior/neurological

polyphagia ( J:155421 )

• higher than normal food intake

• within a week after TM treatment increased food consumption (125%) which continues up to 8 months

poor grooming ( J:155421 )

• 53% (95 of 180) of surviving mice appear ''scruffy'', versus 3% (8 of 244) of wild type

increased startle reflex ( J:155421 )

• enhanced startle response

hyperactivity ( J:155421 )

• most mice (96 of 180) are strikingly hyperkinetic in the open field test

increased locomotor activity ( J:155421 )

• travel 3-fold greater distance in an open field

seizures ( J:155421 )

• 10-fold higher propensity for seizures

tonic-clonic seizures ( J:155421 )

• 3.1% mice (38 of 1,232) have tonic-clonic seizures during routine cage changes and handling of mice, versus 0.3% of wild type mice

adipose tissue

decreased white adipose tissue amount ( J:155421 )

• strikingly lower content of the peritoneal white adipose tissue (WAT), on average only 16% of WAT in wild type mice

decreased abdominal adipose tissue amount ( J:155421 )

• contain little or no visceral fat

decreased brown fat cell size ( J:155421 )

• decrease average diameter of intrascapular brown adipocytes

decreased white fat cell size ( J:155421 )

• the average diameter of WAT adipocytes is 30% of that of the wild type mice

abnormal white adipose tissue physiology ( J:155421 )

• exhibit ectopic induction of the uncoupling protein 1 (Ucp1) in white adipose tissue

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:155421 )

• resistant to high-fat diet induced obesity

impaired adaptive thermogenesis ( J:155421 )

• strongly hypersensitive to cold

decreased circulating glucose level ( J:155421 )

• decreased fasting blood glucose level (88.6 mg/dl versus 125.3 mg/dl)

• lower glucose levels 6 hr after administration of glucose (80.9 mg/dl versus 109.7 mg/dl)

• no other significant differences in blood composition

decreased core body temperature ( J:155421 )

• lower core body temperature on average 35.1C (36.7C in wild type)

cerebral edema ( J:155421 )

• the average water content and dry weight was 80.5% and 19.5%, respectively, versus 79.9% and 20.1% of wild type brains

increased basal metabolism ( J:155421 )

• increased metabolic rate (resting metabolic rate, RMR)

• consume on average 46.12 ml of oxygen per kg per min, versus 29.3 ml of oxygen per kg per min

• decreased expression of mRNA encoding proopiomelanocortin (POMC) in hypothalami

• normal respiratory exchange ratio (RER)

nervous system

seizures ( J:155421 )

• 10-fold higher propensity for seizures

tonic-clonic seizures ( J:155421 )

• 3.1% mice (38 of 1,232) have tonic-clonic seizures during routine cage changes and handling of mice, versus 0.3% of wild type mice

cerebral edema ( J:155421 )

• the average water content and dry weight was 80.5% and 19.5%, respectively, versus 79.9% and 20.1% of wild type brains

increased brain size ( J:155421 )

• brains appear swollen and bigger

increased brain weight ( J:155421 )

• the average brain weight, as a percentage of total body weight (TBW) are 3.09%, versus 1.96% of wild type mice

• no differences in cell proliferation (5-ethynyl-29-deoxyuridine (EdU) incorporation)

skeleton

abnormal cranium morphology ( J:155421 )

• the skulls appear to be thinner and softer

kyphosis ( J:155421 )

• 66% (109 of 180) of surviving mice have a kyphotic posture, versus 2% (5 of 244) of wild type

reproductive system

abnormal spermatid morphology ( J:155421 )

♂ • lumens of seminiferous tubules contain few sperm cells, in a disorganized arrangement

decreased male germ cell number ( J:155421 )

♂ • lumens of seminiferous tubules contain few sperm cells

abnormal testis development ( J:155421 )

♂ • testis extracts contain the 85-kDa fragment of poly(ADP-ribose)-polymerase (PARP) but no full-length PARP, indicating extensive apoptosis

male infertility ( J:155421 )

♂ • males are infertile

cardiovascular system

increased heart weight ( J:155421 )

• hearts are disproportionately large

renal/urinary system

increased kidney weight ( J:155421 )

• kidneys are disproportionately large

cellular

abnormal spermatid morphology ( J:155421 )

♂ • lumens of seminiferous tubules contain few sperm cells, in a disorganized arrangement

decreased male germ cell number ( J:155421 )

♂ • lumens of seminiferous tubules contain few sperm cells

abnormal cell physiology ( J:155421 )

• increased retention of 14C in their brains, livers, spleens, kidneys and hearts

digestive/alimentary system

abnormal intestinal absorption ( J:155421 )

• increased intestinal import of 14C-protein

pigmentation

abnormal coat/hair pigmentation ( J:155421 )

• 10% (8 of 80) of surviving mice develop patches of red hair among their normally black hair

endocrine/exocrine glands

abnormal testis development ( J:155421 )

♂ • testis extracts contain the 85-kDa fragment of poly(ADP-ribose)-polymerase (PARP) but no full-length PARP, indicating extensive apoptosis

craniofacial

abnormal cranium morphology ( J:155421 )

• the skulls appear to be thinner and softer

integument

abnormal coat/hair pigmentation ( J:155421 )

• 10% (8 of 80) of surviving mice develop patches of red hair among their normally black hair

Genotype
MGI:3809283

cn46

• Allelic Composition: Gdnf^tm1Bbd/Gdnf^tm1Jlob; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

nervous system

abnormal brain morphology ( J:139371 )

• tamoxifen treatment leads to the death of catecholaminergic neurons in the brain

abnormal substantia nigra morphology ( J:139371 )

• 210 days after tamoxifen treatment, there is a substantial lose (about 50%) of tyrosine hydroxylase positive neurons in the substantia nigra adult mice

• there is also a drop in the total number of neurons in the substantia nigra after tamoxifen treatment

abnormal tegmentum morphology ( J:139371 )

• 210 days after tamoxifen treatment, there is a substantial lose (about 2.5-fold) of tyrosine hydroxylase positive neurons in the ventral tegmentum of adult mice

• there is also a drop in the total number of neurons in the ventral tegmentum after tamoxifen treatment

abnormal locus ceruleus morphology ( J:139371 )

• neurons are diminished in the locus ceruleus 210 days after tamoxifen treatment

abnormal dorsal striatum morphology ( J:139371 )

• fiber density of tyrosine hydroxylase positive neurons are diminished 210 days after tamoxifen treatment

abnormal ventral striatum morphology ( J:139371 )

• fiber density of tyrosine hydroxylase positive neurons are diminished 210 days after tamoxifen treatment

behavior/neurological

decreased locomotor activity ( J:139371 )

• 100 days after tamoxifen injection, mice have reduced activity in open field tests with about 25% less activity

• resting time of mice in open field tests increases significantly 100 days after tamoxifen treatment

• this hypoactivity worsens with the passage of time

cardiovascular system

abnormal carotid body morphology ( J:139371 )

• tyrosine hydroxylase positive neurons are diminished by more than half 210 days after tamoxifen-treatment

Genotype
MGI:4839181

cn47

• Allelic Composition: Rapgef2^tm1.1Hous/Rapgef2^tm1.1Hous; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:165879 )

• most mice treated with tamoxifen at E11.5 and E13.5 die E17.5 and E18.5 with remaining mice dying at E19.5 to E10.5

• however, mice treated with tamoxifen at E17.5 and E19.5 exhibit the same lethality as in similarly treated Rapgef2^tm1.1Hous homozygotes

hematopoietic system

abnormal definitive hematopoiesis ( J:165879 )

• mice treated with tamoxifen at E11.5 and E13.5 exhibit impaired fetal liver hematopoiesis with reduced differentiation of erythroid progenitor cells compared with similarly treated Rapgef2^tm1.1Hous homozygotes

decreased erythroid progenitor cell number ( J:165879 )

• at E16.5 in the livers of mice treated with tamoxifen at E11.5 and E13.5

cardiovascular system

abnormal vascular development ( J:165879 )

• at E17.5, mice treated with tamoxifen at E11.5 and E13.5 lack major embryonic blood vessels unlike wild-type mice

growth/size/body

decreased birth body size ( J:165879 )

• in mice treated with tamoxifen at E17.5 and E19.5

liver/biliary system

pale liver ( J:165879 )

• at E16.5 in mice treated with tamoxifen at E11.5 and E13.5

integument

pallor ( J:165879 )

• at E17.5 in mice treated with tamoxifen at E11.5 and E13.5

Genotype
MGI:5440734

cn48

• Allelic Composition: Wnt5a^tm1.1Tpy/Wnt5a^tm1.1Tpy; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

digestive/alimentary system

abnormal intestine regeneration ( J:187747 )

• abnormal wound channels containing fewer invaginations at day 6 and lacking crypt like structures at day 8 are seen after colonic mucosal injury in tamoxifen treated mice

homeostasis/metabolism

abnormal wound healing ( J:187747 )

• abnormal wound channels containing fewer invaginations at day 6 and lacking crypt like structures at day 8 are seen after colonic mucosal injury in tamoxifen treated mice

Genotype
MGI:3693848

cn49

• Allelic Composition: Six3^tm2Gco/Six3^tm2.1Gco; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

vision/eye

abnormal lens morphology ( J:116102 )

abnormal lens development ( J:116102 )

• defects are observed starting at E10.5

• reduction in size of invaginating lens pit is observed in mildly and moderately affected embryos

• at E14.5, some embryos have an abnormally persistent lens stalk

• differentiation of lens is not affected in mildly or moderately affected mutant lenses

abnormal lens induction ( J:116102 )

• in severely affected lenses at E10.5, no lens-like structures are present

abnormal lens vesicle development ( J:116102 )

• at E12.5, in mild cases, lens vesicle is small but relatively normal, small and abnormal in moderated cases and completely absent in severely affected embryos and neuroretinal is malformed also

abnormal lens fiber morphology ( J:116102 )

• at E14.5 some embryos show disorganized lens fibers

aphakia ( J:116102 )

• lens is absent in some mutants

cataract ( J:116102 )

• cataracts are present in some mice

small lens ( J:116102 )

• some mice show drastically reduced lens size

abnormal optic vesicle formation ( J:116102 )

• shape of vesicle is defective

Genotype
MGI:3842509

cn50

• Allelic Composition: Kmt5a^tm1.1Dare/Kmt5a^tm1.2Dare; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA * SJL

cellular

abnormal cell physiology ( J:147765 )

• tamoxifen-treated embryonic stem cells exhibit global chromosomal decondensation at interphase compared to in wild-type cells

abnormal cell cycle checkpoint function ( J:147765 )

• tamoxifen-treated embryonic stem cells exhibit a defect in cell growth at G2/M phase unlike wild-type cells

increased apoptosis ( J:147765 )

• 24 hours after tamoxifen treatment, embryonic stem cells undergo apoptosis unlike wild-type cells

abnormal DNA repair ( J:147765 )

• tamoxifen-treated embryonic stem cells exhibit increased DNA damage compared to wild-type cells

decreased DNA replication ( J:147765 )

• tamoxifen-treated embryonic stem cells exhibit decreased DNA synthesis compared to in wild-type cells

homeostasis/metabolism

abnormal DNA repair ( J:147765 )

• tamoxifen-treated embryonic stem cells exhibit increased DNA damage compared to wild-type cells

decreased DNA replication ( J:147765 )

• tamoxifen-treated embryonic stem cells exhibit decreased DNA synthesis compared to in wild-type cells

Genotype
MGI:5301413

cn51

• Allelic Composition: Mecom^tm1Aspe/Mecom^tm2.1Aspe; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/SvImJ * C57BL/6 * C57BL/6J * CBA

hematopoietic system

abnormal bone marrow cell morphology/development ( J:178429 )

• tamoxifen-treated mice lack long-term repopulating cells (or high proliferative potential colony-forming cells; HPP-CFC) unlike wild-type mice

abnormal common myeloid progenitor cell morphology ( J:178429 )

• granulocyte and macrophage progenitors (CFU-G and CFU-M, respectively) are increase compared with wild-type mice

decreased common myeloid progenitor cell number ( J:178429 )

• tamoxifen-treated mice exhibit fewer multipotent progenitors (CFU-GEMM) and granulocyte-macrophage progenitor (CFU-GM) compared with wild-type mice

Genotype
MGI:5301414

cn52

• Allelic Composition: Mecom^tm2.1Aspe/Mecom^tm2.1Aspe; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/SvImJ * C57BL/6 * CBA

hematopoietic system

abnormal bone marrow cell morphology/development ( J:178429 )

• tamoxifen-treated mice lack long-term repopulating cells (or high proliferative potential colony-forming cells; HPP-CFC) unlike wild-type mice

abnormal common myeloid progenitor cell morphology ( J:178429 )

• granulocyte and macrophage progenitors (CFU-G and CFU-M, respectively) are increase 3- to 4-fold compared with wild-type mice

decreased common myeloid progenitor cell number ( J:178429 )

• tamoxifen-treated mice exhibit fewer multipotent progenitors (CFU-GEMM) and granulocyte-macrophage progenitor (CFU-GM) compared with wild-type mice

Genotype
MGI:5086257

cn53

• Allelic Composition: Cxadr^tm1.1Ics/Cxadr^tm1.1Ics; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/6J * CBA

behavior/neurological

abnormal response to new environment ( J:174138 )

• mice treated with tamoxifen at 4 weeks of age show a reduced tendency to freeze when transferred to a novel environment

cardiovascular system

abnormal intercalated disk morphology ( J:174138 )

• most discs are severely changed with disconnection between myofilaments and the presence of big vacuoles-containing parts of membranes in tamoxifen treated mice

• the outline of the junction is also changed with the distance between zonula adherens being wider and containing clot like contents in some areas

atrioventricular block ( J:174138 )

• complete atrioventricular block with temporal dissociation between atrial depolarization and ventricular depolarization in mice treated with tamoxifen at 4 weeks of age at 24 weeks after the last tamoxifen treatment

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:174138 )

• atrophy and metaplastic phenotype are present as early as 3 weeks after tamoxifen treatment and is maintained up to 18 months after tamoxifen treatment

decreased pancreatic acinar cell number ( J:174138 )

• almost a complete lack of acinar cells in mice treated with tamoxifen at 4 weeks of age

exocrine pancreas atrophy ( J:174138 )

• in mice treated with tamoxifen at 4 weeks of age

abnormal intestine morphology ( J:174138 )

• dilated intestine in mice treated with tamoxifen at 4 weeks of age at up to 18 months after the last tamoxifen treatment

endocrine/exocrine glands

enlarged thymus ( J:174138 )

• in tamoxifen treated mice 2 -3 days after the last treatment

increased thymocyte number ( J:174138 )

• in tamoxifen treated mice 2 -3 days after the last treatment

abnormal pancreas morphology ( J:174138 )

• in mice treated with tamoxifen at 4 weeks of age the pancreas consists of mainly adipose tissue in which apparently normal islets of Langerhans are interspersed

abnormal exocrine pancreas morphology ( J:174138 )

• atrophy and metaplastic phenotype are present as early as 3 weeks after tamoxifen treatment and is maintained up to 18 months after tamoxifen treatment

decreased pancreatic acinar cell number ( J:174138 )

• almost a complete lack of acinar cells in mice treated with tamoxifen at 4 weeks of age

exocrine pancreas atrophy ( J:174138 )

• in mice treated with tamoxifen at 4 weeks of age

small pancreas ( J:174138 )

• dramatically smaller in mice treated with tamoxifen at 4 weeks of age at up to 18 months after the last tamoxifen treatment

pancreatic acinar-to-ductal metaplasia ( J:174138 )

• duct-like tubular complexes replace the acinar cells in mice treated with tamoxifen at 4 weeks of age

hematopoietic system

enlarged thymus ( J:174138 )

• in tamoxifen treated mice 2 -3 days after the last treatment

increased thymocyte number ( J:174138 )

• in tamoxifen treated mice 2 -3 days after the last treatment

immune system

enlarged thymus ( J:174138 )

• in tamoxifen treated mice 2 -3 days after the last treatment

increased thymocyte number ( J:174138 )

• in tamoxifen treated mice 2 -3 days after the last treatment

muscle

abnormal intercalated disk morphology ( J:174138 )

• most discs are severely changed with disconnection between myofilaments and the presence of big vacuoles-containing parts of membranes in tamoxifen treated mice

• the outline of the junction is also changed with the distance between zonula adherens being wider and containing clot like contents in some areas

Genotype
MGI:5469879

cn54

• Allelic Composition: Syngap1^tm2Geno/Syngap1⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

behavior/neurological

abnormal behavior ( J:193208 )

• mice exhibit behavioral abnormalities as in Syngap1^tm1Rlh heterozygotes

abnormal spatial working memory ( J:193208 )

• untreated mice and mice treated with tamoxifen in adulthood exhibit absence of spontaneous alteration in a T-maze compared with control mice

decreased anxiety-related response ( J:193208 )

• untreated mice and mice treated with tamoxifen in adulthood spend increased time in open arms of an elevated plus maze compared with control mice

hyperactivity ( J:193208 )

• untreated mice and mice treated with tamoxifen in adulthood exhibit increased activity in an open field compared with control mice

Genotype
MGI:5549958

cn55

• Allelic Composition: Alkbh4^tm1Geno/Alkbh4^tm1Geno; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

cellular

abnormal centrosome morphology ( J:205739 )

• increased centrosome number is likely a consequence of polyploidy caused by cells failing to go through cytokinesis

increased cell nucleus count ( J:205739 )

• increased frequency of multinucleation in tamoxifen-treated mouse embryonic fibroblasts due to aborted cytokinesis

abnormal mitotic cytokinesis ( J:205739 )

• tamoxifen-treated mouse embryonic fibroblasts exhibit defects in the organization of the cleavage furrow, increased frequency of multinucleation due to aborted cytokinesis and increased centrosomes number likely a consequence of polyploidy compared with control cells

• however, complementation with the wild-type protein rescues cytokinesis defects

decreased fibroblast cell migration ( J:205739 )

• in tamoxifen-treated mouse embryonic fibroblasts

Genotype
MGI:5316225

cn56

• Allelic Composition: Atr^tm2Bal/Atr^tm2Bal; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

cellular

abnormal neuron proliferation ( J:181920 )

• decrease in proliferation in cultured neurospheres after 4OHT treatment

nervous system

abnormal neuron proliferation ( J:181920 )

• decrease in proliferation in cultured neurospheres after 4OHT treatment

Genotype
MGI:5468350

cn57

• Allelic Composition: Ccnd1^tm1Wbg/Ccnd1^tm5.1Pisc; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

normal phenotype

no abnormal phenotype detected ( J:192032 )

• tamoxifen-treated mice exhibit no obvious abnormalities

Genotype
MGI:5468352

cn58

• Allelic Composition: Ccnd1^tm1Wbg/Ccnd1^tm5.1Pisc; Tg(CAG-cre/Esr1*)5Amc/0; Tg(MMTV-Erbb2)NK1Mul/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA * FVB/N

neoplasm

decreased tumor growth/size ( J:192032 )

• tamoxifen-treatment halts cancer progression and lowers tumor burden with increased senescence of tumor cells compared to in control mice

Genotype
MGI:5308067

cn59

• Allelic Composition: Esco2^tm1.1Ge/Esco2^tm1.1Ge; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA * SJL

cellular

abnormal cell nucleus morphology ( J:180371 )

• tamoxifen-treated mouse embryonic fibroblasts exhibit highly abnormal nuclear morphology with micronuclei and multilobulated nuclei

abnormal chromosome morphology ( J:180371 )

• chromosomes from tamoxifen-treated mouse embryonic fibroblasts exhibit railroad track morphology

abnormal mitosis ( J:180371 )

• tamoxifen-treated mouse embryonic fibroblasts exhibit lagging chromosomes with reduced pericentric heterochromatin cohesion

increased mitotic index ( J:180371 )

• tamoxifen-treated mouse embryonic fibroblasts exhibit a 2.5-fold increase in mitotic index in asynchronously grown cultures

decreased cell proliferation ( J:180371 )

• tamoxifen-treated mouse embryonic fibroblasts fail to proliferate

Genotype
MGI:6192377

cn60

• Allelic Composition: Kdm6a^tm1Cdcn/Y; Tg(CAG-cre/Esr1*)5Amc/0; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * CBA * FVB/N

mortality/aging

premature death ( J:263565 )

• tamoxifen-treated mice have a median survival of 3.8 months

neoplasm

increased chronic myelocytic leukemia incidence ( J:263565 )

• tamoxifen treated mice develop chronic myelomonocytic leukemia-like disease with a shorter latency than single Kdm6a mutants

hematopoietic system

enlarged spleen ( J:263565 )

• splenomegaly develops 3 months after tamoxifen injection

anemia ( J:263565 )

• in tamoxifen treated mice

increased granulocyte monocyte progenitor cell number ( J:263565 )

• increase in number of granulocyte-macrophage progenitor (GMP) cells in the bone marrow of tamoxifen treated mice

decreased erythrocyte cell number ( J:263565 )

• decrease in number of red blood cells in tamoxifen treated mice which is greater than in either single mutant

increased neutrophil cell number ( J:263565 )

• expansion of neutrophils in the spleen, bone marrow, liver and peripheral blood of tamoxifen treated mice

thrombocytopenia ( J:263565 )

• decrease in number of platelets in tamoxifen treated mice which is greater than in either single mutant

increased monocyte cell number ( J:263565 )

• increase in the number of monocytes in tamoxifen treated mice, which is much greater than in either single mutant

increased myeloid cell number ( J:263565 )

• expansion of myeloid cells in the spleen, bone marrow, liver, and peripheral blood of tamoxifen treated mice

increased hematopoietic stem cell number ( J:263565 )

• an increase in the number and proportion of hematopoietic stem cells (HSCs) in the bone marrow of tamoxifen treated mice, however the number of bone marrow cells is normal

immune system

enlarged spleen ( J:263565 )

• splenomegaly develops 3 months after tamoxifen injection

increased neutrophil cell number ( J:263565 )

• expansion of neutrophils in the spleen, bone marrow, liver and peripheral blood of tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• increase in the number of monocytes in tamoxifen treated mice, which is much greater than in either single mutant

growth/size/body

enlarged spleen ( J:263565 )

• splenomegaly develops 3 months after tamoxifen injection

Genotype
MGI:3795455

cn61

• Allelic Composition: Cdc73^tm1Btt/Cdc73^tm1Btt; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

mortality/aging

premature death ( J:135255 )

• mice die 20 days after administration of tamoxifen

prenatal lethality, complete penetrance ( J:135255 )

• when tamoxifen is administered from E8.5 to E14.5

cellular

increased apoptosis ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit an increase in apoptotic cells in the salivary glands, tongue, stomach, intestine, liver and kidneys compared to in wild-type mice

increased fibroblast apoptosis ( J:135255 )

• mouse embryonic fibroblast cells treated with tamoxifen exhibit increased apoptosis compared to wild-type cells

hepatic necrosis ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit necrotic cells in the liver and kidney likely due to multiorgan failure

renal necrosis ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit necrotic cells in the liver and kidney likely due to multiorgan failure

decreased cell proliferation ( J:135255 )

• in mouse embryonic fibroblast cells treated with tamoxifen

digestive/alimentary system

abnormal digestive system morphology ( J:135255 )

• after treatment of adults with tamoxifen, some mice develop dilation of the gastrointestinal tract

small salivary gland ( J:135255 )

• after treatment of adults with tamoxifen

small stomach ( J:135255 )

• after treatment of adults with tamoxifen

endocrine/exocrine glands

small salivary gland ( J:135255 )

• after treatment of adults with tamoxifen

small seminal vesicle ( J:135255 )

♂ • after treatment of adults with tamoxifen

small testis ( J:135255 )

♂ • after treatment of adults with tamoxifen

abnormal gland physiology ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit reduced submandibular and seminal vesicle secretion and a decrease in the number of tubular glands compared to wild-type mice

liver/biliary system

hepatic necrosis ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit necrotic cells in the liver and kidney likely due to multiorgan failure

small liver ( J:135255 )

• after treatment of adults with tamoxifen

renal/urinary system

renal necrosis ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit necrotic cells in the liver and kidney likely due to multiorgan failure

small kidney ( J:135255 )

• after treatment of adults with tamoxifen

respiratory system

small lung ( J:135255 )

• after treatment of adults with tamoxifen

decreased pulmonary respiratory rate ( J:135255 )

• after treatment of adults with tamoxifen, breathing is labored

homeostasis/metabolism

ascites ( J:135255 )

• after treatment of adults with tamoxifen, some mice develop ascites

nervous system

abnormal nervous system development ( J:135255 )

• when tamoxifen is administered from E8.5 to E14.5, development of the central nervous system is significantly delayed compared to in wild-type mice

behavior/neurological

abnormal reflex ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit slow reactions

decreased locomotor activity ( J:135255 )

• after treatment of adults with tamoxifen

muscle

decreased skeletal muscle mass ( J:135255 )

• after treatment of adults with tamoxifen, mice exhibit muscle loss

adipose tissue

decreased subcutaneous adipose tissue amount ( J:135255 )

• after treatment of adults with tamoxifen

decreased abdominal adipose tissue amount ( J:135255 )

• after treatment of adults with tamoxifen

embryo

decreased embryo size ( J:135255 )

• when tamoxifen is administered from E8.5 to E14.5, E10.5 and E12.5 or E12.5 and E14.5, embryos are smaller than normal

reproductive system

small seminal vesicle ( J:135255 )

♂ • after treatment of adults with tamoxifen

small testis ( J:135255 )

♂ • after treatment of adults with tamoxifen

hematopoietic system

small spleen ( J:135255 )

• after treatment of adults with tamoxifen

immune system

small spleen ( J:135255 )

• after treatment of adults with tamoxifen

growth/size/body

decreased embryo size ( J:135255 )

• when tamoxifen is administered from E8.5 to E14.5, E10.5 and E12.5 or E12.5 and E14.5, embryos are smaller than normal

weight loss ( J:135255 )

• after treatment of adults with tamoxifen

cardiovascular system

small heart ( J:135255 )

• after treatment of adults with tamoxifen

integument

decreased subcutaneous adipose tissue amount ( J:135255 )

• after treatment of adults with tamoxifen

Genotype
MGI:6220878

cn62

• Allelic Composition: Trpm7^tm1Clph/Trpm7^tm1Clph; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

Representative images of grossly deformed, nonviable Trpm7^tm1Clph/Trpm7^tm1Clph Tg(CAG-cre/Esr1*)5Amc/0 embryos at E9.5 and E10.5

mortality/aging

embryonic lethality, complete penetrance ( J:181963 )

• when a single tamoxifen dose (25 ug/g of body weight) is injected into pregnant females at early gestation stages (E7-E9), all embryos die within 48-72 hrs of treatment

embryo

abnormal developmental patterning ( J:181963 )

• following tamoxifen injection at E7-E9, dying embryos exhibit abnormal body patterning

abnormal embryo morphology ( J:181963 )

• following tamoxifen injection at E7-E9, non-viable embryos are grossly deformed at E9.5 and E10.5

normal phenotype

no abnormal phenotype detected ( J:181963 )

• following a single tamoxifen injection (25 ug/g of body weight) at E14.5, live pups are born in normal ratios, with no dead embryos found in utero 48 hrs after injection

• a single tamoxifen injection (50 ug/g of body weight) into 6-wk-old mice results in normal survival with grossly normal adult mice at 1-2 months after injection

• following 3 daily tamoxifen injections (25-50 ug/g of body weight) into 4-wk-old mice, all adult mice show normal kidney, heart, and liver histology at 4 weeks after injection

Genotype
MGI:4453345

cn63

• Allelic Composition: Lhx2^tm1.1Lcar/Lhx2^tm1Dra; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

Hair follicles of tamoxifen-treated Lhx2^tm1.1Lcar/Lhx2^tm1Dra Tg(CAG-cre/Esr1*)5Amc/0 mice arrest during anagen progression and are unable to assemble a normal hair shaft

integument

abnormal hair growth ( J:159209 )

• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair

abnormal hair cycle anagen phase ( J:159209 )

• unable to develop beyond Sub-stage III and assemble a normal hair shaft

Genotype
MGI:5490597

cn64

• Allelic Composition: Nrl^tm1Jcco/Nrl^tm1Jcco; Rho^tm1Jlem/Rho^tm1Jlem; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

Rod reprogramming prevents retinal degeneration in tamoxifen treated Rho^tm1Jlem/Rho^tm1Jlem Nrl^tm1Jcco/Nrl^tm1Jcco Tg(CAG-cre/Esr1*)5Amc/0 mice

vision/eye

vision/eye phenotype ( J:193697 )

N • photoreceptor death observed in Rho^tm1Jlem homozygotes is prevented in tamoxifen-treated mice with preservation of rod cell bodies and inner segments and intact photopic b-wave over a wide range of flash intensities

Genotype
MGI:5473527

cn65

• Allelic Composition: Pomc^tm2Low/Pomc^tm2Low; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

Obesity in Pomc^tm2Low/Pomc^tm2Low Tg(CAG-cre/Esr1*)5Amc/0 females and weight loss following tamoxifen treatment

growth/size/body

increased lean body mass ( J:194013 )

• in vehicle treated mice

increased body length ( J:194013 )

• in vehicle treated mice

abnormal body weight ( J:194013 )

• mice treated with tamoxifen at P60 or P180 exhibit rapid weight loss for 3 weeks followed by a plateau and resumption of weight gain

increased body weight ( J:194013 )

• in vehicle-treated mice

• in male mice treated with tamoxifen at P60 or P180

• however, mice exhibit normal weight when with tamoxifen at P25 exhibit normal weight or when male mice are subjected to caloric restriction and returned to ad libitum feeding with tamoxifen treatment at P60

increased susceptibility to weight gain ( J:194013 )

• in vehicle-treated mice

• in male mice treated with tamoxifen at P60 or P180

• however, mice exhibit normal weight when with tamoxifen at P25 exhibit normal weight or when male mice are subjected to caloric restriction and returned to ad libitum feeding with tamoxifen treatment at P60

increased liver weight ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment restores liver weight

homeostasis/metabolism

increased circulating glucose level ( J:194013 )

• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180

increased circulating insulin level ( J:194013 )

• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180

increased circulating leptin level ( J:194013 )

• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180

decreased oxygen consumption ( J:194013 )

• regardless of tamoxifen treatment

insulin resistance ( J:194013 )

• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180

adipose tissue

increased total body fat amount ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment restores body fat

increased gonadal fat pad weight ( J:194013 )

♂ • in vehicle treated male mice

♂ • however, tamoxifen treatment at P25, P60 or P180 restores fat pad weight

increased inguinal fat pad weight ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment at P25, P60 or P180 restores fat pad weight

increased retroperitoneal fat pad weight ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment at P60 or P180 restores fat pad weight

behavior/neurological

decreased food intake ( J:194013 )

• in the first 2 to 3 weeks following tamoxifen-treatment

decreased compensatory feeding amount ( J:194013 )

• following a 24 hour fast in vehicle treated mice

• however, tamoxifen restores fast-induced hyperphagia

polyphagia ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment at P25, P60 or P180 restores daily food intake

decreased locomotor activity ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment restores activity

liver/biliary system

increased liver weight ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment restores liver weight

hepatic steatosis ( J:194013 )

• in vehicle treated mice

• however, tamoxifen treatment restores liver fat content

Genotype
MGI:4453347

cn66

• Allelic Composition: Lhx2^tm1.1Lcar/Lhx2^tm1.1Lcar; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

integument

abnormal hair growth ( J:159209 )

• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair

abnormal hair cycle anagen phase ( J:159209 )

• unable to develop beyond Sub-stage III and assemble a normal hair shaft

Genotype
MGI:4868430

cn67

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1.1Khol; Mmp15^tm1Kohl/Mmp15^tm1Kohl; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA

embryo

abnormal placental labyrinth vasculature morphology ( J:167396 )

• mice treated with tamoxifen at E7.5 exhibit compact structure, sparse vessels, and multiple dead cells around the fetal blood vessels unlike in wild-type mice

absent placental labyrinth ( J:167396 )

• at E12.5 in tamoxifen-treated mice starting at E7.5

• however, placenta develops normally in mice treated with tamoxifen at E12.5

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:167396 )

N • tamoxifen-treated mice exhibit normal mammary gland involution

cardiovascular system

abnormal placental labyrinth vasculature morphology ( J:167396 )

• mice treated with tamoxifen at E7.5 exhibit compact structure, sparse vessels, and multiple dead cells around the fetal blood vessels unlike in wild-type mice

Genotype
MGI:5523415

cn68

• Allelic Composition: Pappa^tm1Lex/Pappa^tm1Lex; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6 * CBA

cardiovascular system

abnormal vascular wound healing ( J:201775 )

• reduced neointima formation following carotid ligation in tamoxifen-treated mice

• however, media area is normal

homeostasis/metabolism

abnormal vascular wound healing ( J:201775 )

• reduced neointima formation following carotid ligation in tamoxifen-treated mice

• however, media area is normal

Genotype
MGI:3793292

cn69

• Allelic Composition: Egln1^tm1Kael/Egln1^tm1Kael; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

mortality/aging

premature death ( J:132718 )

• mutants exposed to tamoxifen at E17.5 and 3 weeks after birth to induce cre expression begin dying suddenly around 10 weeks of age

growth/size/body

decreased body size ( J:132718 )

• by 10 weeks of age, mutants that are exposed to tamoxifen at E17.5 and 3 weeks after birth, are smaller

cardiovascular system

blood vessel congestion ( J:132718 )

• 8- to 10-week old mutants treated with tamoxifen at E17.5 and 3 weeks after birth exhibit venous congestion

abnormal myocardium layer morphology ( J:132718 )

• the space between myocardial fibers is increased in mutants treated with tamoxifen at E17.5 and 3 weeks after birth

increased myocardial fiber size ( J:132718 )

• cardiomyocytes of mutants treated with tamoxifen at E17.5 and 3 weeks after birth are enlarged, with occasional large nuclei

dilated cardiomyopathy ( J:132718 )

• mutants treated with tamoxifen at E17.5 and 3 weeks after birth consistently exhibit dilated cardiomyopathy

cardiac ischemia ( J:132718 )

• mutants treated with tamoxifen at E17.5 and 3 weeks after birth exhibit increased contraction band necrosis indicative of early cardiac ischemia

hemorrhage ( J:132718 )

• retroperitoneal hemorrhage is observed by 10 weeks of age in mutants exposed to tamoxifen at E17.5 and 3 weeks after birth

hematopoietic system

polycythemia ( J:132718 )

• mutants treated with tamoxifen at E17.5 and 3 weeks after birth show profound increases in red blood cell production associated with increased serum erythropoietin levels

muscle

abnormal myocardium layer morphology ( J:132718 )

• the space between myocardial fibers is increased in mutants treated with tamoxifen at E17.5 and 3 weeks after birth

increased myocardial fiber size ( J:132718 )

• cardiomyocytes of mutants treated with tamoxifen at E17.5 and 3 weeks after birth are enlarged, with occasional large nuclei

dilated cardiomyopathy ( J:132718 )

• mutants treated with tamoxifen at E17.5 and 3 weeks after birth consistently exhibit dilated cardiomyopathy

integument

reddish skin ( J:132718 )

• by 10 weeks of age, mutants that are exposed to tamoxifen at E17.5 and 3 weeks after birth are erythematous and begin dying suddenly

homeostasis/metabolism

increased circulating erythropoietin level ( J:132718 )

• mutants treated with tamoxifen at E17.5 and 3 weeks after birth show profound increases in red blood cell production associated with increased serum erythropoietin levels

Genotype
MGI:4429150

cn70

• Allelic Composition: Ewsr1^tm1Sblee/Ewsr1⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

normal phenotype

no abnormal phenotype detected ( J:156860 )

• no effects on survival even after 6 months following tamoxifien injection

• no phenotype of MEFS with tamoxifen

Genotype
MGI:4429149

cn71

• Allelic Composition: Ewsr1^{tm2(FLI1*)Sblee}/Ewsr1⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

mortality/aging

premature death ( J:156860 )

• after tamoxifen injection, within 4 to 6 days mice become moribund and die

cellular

increased fibroblast apoptosis ( J:156860 )

• 24 hours after tamoxifen application MEF cultures begin to die and caspase-3 activity increases

increased renal tubule apoptosis ( J:156860 )

• after tamoxifen injection, increase in TUNEL+ cells in epithelia

renal/urinary system

increased renal tubule apoptosis ( J:156860 )

• after tamoxifen injection, increase in TUNEL+ cells in epithelia

Genotype
MGI:5296661

cn72

• Allelic Composition: Kdm5a^tm1Kael/Kdm5a^tm1Kael; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

cellular

early cellular replicative senescence ( J:175625 )

• in mouse embryonic fibroblasts treated with tamoxifen

Genotype
MGI:3845013

cn73

• Allelic Composition: Ptpn11^tm6Bgn/Ptpn11⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

hematopoietic system

abnormal definitive hematopoiesis ( J:148430 )

• following tamoxifen treatment cultured bone marrow megakaryocyte-erythrocyte progenitor cells produce significantly fewer erythrocyte colony-forming unit colonies and slightly more erythroid burst-forming unit colonies

abnormal leukopoiesis ( J:148430 )

• following tamoxifen treatment cultured granulocyte-monocyte progenitor cells and common myeloid progenitor cells give rise to more cytokine independent colonies

immune system

abnormal leukopoiesis ( J:148430 )

• following tamoxifen treatment cultured granulocyte-monocyte progenitor cells and common myeloid progenitor cells give rise to more cytokine independent colonies

Genotype
MGI:5707476

cn74

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0; Wee1^tm1Cxd/Wee1^tm1Cxd
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

cellular

abnormal cell morphology ( J:228492 )

• mouse embryonic fibroblasts treated with tamoxifen exhibit nuclear fragmentation and membrane blebbing with rounding and detaching from the culture plate unlike control cells

abnormal cell cycle checkpoint function ( J:228492 )

• defective G2/M checkpoint in mouse embryonic fibroblasts treated with tamoxifen

increased apoptosis ( J:228492 )

• in mouse embryonic fibroblasts treated with tamoxifen

Genotype
MGI:5305780

cn75

• Allelic Composition: Gak^tm2Legr/Gak^tm2Legr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

mortality/aging

premature death ( J:180119 )

• mice die within six days of tamoxifen treatment

Genotype
MGI:5688888

cn76

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

cardiovascular system

abnormal retina vasculature morphology ( J:221181 )

• the capillary network of the intermediate and deep plexus is denser in tamoxifen treated mutants than in controls

• retinal capillaries of tamoxifen treated mice are surrounded by 1-2 complete layers of smooth muscle-like cells that are completely surrounded by a basal lamina that is thicker than in controls compared to controls in which pericytes share the basal lamina with endothelial cells

• marker analysis indicates endothelial cell loss in the retinal vasculature of tamoxifen treated mice

• proliferative retinopathy in tamoxifen treated mice results in the formation of epiretinal vascular membranes on the surface of the retina that are not seen in controls

abnormal retina blood vessel morphology ( J:221181 )

• dilation of retinal vessels and tortuous vessels with massive vascular leakage are seen in tamoxifen treated mice at 4 weeks of age

• retinal vessels of tamoxifen treated mice show the presence of numerous caveolae along the luminal cell membrane of their endothelial cells

• many capillaries in the outer plexiform layer show a narrowed or absent lumen and the opposing vascular walls of capillaries are often in contact with each other in tamoxifen treated mice

retina microaneurysm ( J:221181 )

• capillary microaneurysms are seen in close association with retinal capillaries throughout the retina of tamoxifen treated mice

• microaneurysms originate laterally from capillaries or are localized at the blind-ending tips of capillaries, have a wide lumen frequently filled with erythrocytes, and are found in capillaries form all three (superficial, intermediate, and deep) vascular plexus of the retina

retina neovascularization ( J:221181 )

• retina shows neovascularization into the vitreous of tamoxifen treated mice

abnormal pericyte morphology ( J:221181 )

• retinal capillaries of tamoxifen treated mice are not covered by differentiated pericytes but by a coat of vascular smooth muscle-like cells, indicating lack of pericyte differentiation

retina hemorrhage ( J:221181 )

• accumulations of erythrocytes between perikarya of retina neurons are seen in tamoxifen treated mutants, indicating intraretinal hemorrhage

• regional hemorrhages are seen between photoreceptor outer segments and cells of the retinal pigment epithelium of tamoxifen treated mice

vitreous body hemorrhage ( J:221181 )

• in tamoxifen treated mice

vision/eye

vitreous body hemorrhage ( J:221181 )

• in tamoxifen treated mice

increased retina apoptosis ( J:221181 )

• increase in neuronal apoptotic cell death in the retina of tamoxifen treated mice

persistence of hyaloid vascular system ( J:221181 )

• hyaloid vessels are still detectable in 8 week old tamoxifen treated mice, indicating persistence of the hyaloid vasculature

abnormal retina morphology ( J:221181 )

• tamoxifen treated mice show numerous white areas on the retina which form fluffy white patches or are dot-like at 8 weeks of age and look like hard exudates and cotton wool spots seen in humans with diabetic retinopathy

• tamoxifen treated mice show capillaries that penetrate the inner limiting membrane of the retina and grow into the vitreous body to cause proliferative retinopathy at about 6 weeks of age

abnormal retina vasculature morphology ( J:221181 )

• the capillary network of the intermediate and deep plexus is denser in tamoxifen treated mutants than in controls

• retinal capillaries of tamoxifen treated mice are surrounded by 1-2 complete layers of smooth muscle-like cells that are completely surrounded by a basal lamina that is thicker than in controls compared to controls in which pericytes share the basal lamina with endothelial cells

• marker analysis indicates endothelial cell loss in the retinal vasculature of tamoxifen treated mice

• proliferative retinopathy in tamoxifen treated mice results in the formation of epiretinal vascular membranes on the surface of the retina that are not seen in controls

abnormal retina blood vessel morphology ( J:221181 )

• dilation of retinal vessels and tortuous vessels with massive vascular leakage are seen in tamoxifen treated mice at 4 weeks of age

• retinal vessels of tamoxifen treated mice show the presence of numerous caveolae along the luminal cell membrane of their endothelial cells

• many capillaries in the outer plexiform layer show a narrowed or absent lumen and the opposing vascular walls of capillaries are often in contact with each other in tamoxifen treated mice

retina microaneurysm ( J:221181 )

• capillary microaneurysms are seen in close association with retinal capillaries throughout the retina of tamoxifen treated mice

• microaneurysms originate laterally from capillaries or are localized at the blind-ending tips of capillaries, have a wide lumen frequently filled with erythrocytes, and are found in capillaries form all three (superficial, intermediate, and deep) vascular plexus of the retina

retina neovascularization ( J:221181 )

• retina shows neovascularization into the vitreous of tamoxifen treated mice

retina hemorrhage ( J:221181 )

• accumulations of erythrocytes between perikarya of retina neurons are seen in tamoxifen treated mutants, indicating intraretinal hemorrhage

• regional hemorrhages are seen between photoreceptor outer segments and cells of the retinal pigment epithelium of tamoxifen treated mice

abnormal retina layer morphology ( J:221181 )

• tamoxifen treated mice show loss of the layered structure of the sensory retina

abnormal retina neuronal layer morphology ( J:221181 )

• tamoxifen treated mice show loss of retinal neurons

decreased retina ganglion cell number ( J:221181 )

• tamoxifen treated mice show reduced retinal ganglion cell numbers

thin retina outer nuclear layer ( J:221181 )

• thickness of the outer nuclear layer is reduced in tamoxifen treated mice

retina detachment ( J:221181 )

• 4 month old mice treated with tamoxifen often exhibit detachment of the sensory retina which remains in contact with the underlying retinal pigment epithelium by thin strands of presumably glial tissue

abnormal electroretinogram waveform feature ( J:221181 )

• tamoxifen treated mice show a reduction in b-wave/a-wave amplitude ratio that indicates a more pronounced inner retinal function loss

decreased a-wave amplitude ( J:221181 )

• in tamoxifen treated mice

decreased b-wave amplitude ( J:221181 )

• in tamoxifen treated mice

hematopoietic system

microgliosis ( J:221181 )

• retinal capillaries are surrounded by reactive microglial cells in tamoxifen treated mice

homeostasis/metabolism

hypoxia ( J:221181 )

• marker analysis indicates retinal hypoxia in tamoxifen treated mice

immune system

microgliosis ( J:221181 )

• retinal capillaries are surrounded by reactive microglial cells in tamoxifen treated mice

nervous system

microgliosis ( J:221181 )

• retinal capillaries are surrounded by reactive microglial cells in tamoxifen treated mice

decreased retina ganglion cell number ( J:221181 )

• tamoxifen treated mice show reduced retinal ganglion cell numbers

cellular

increased retina apoptosis ( J:221181 )

• increase in neuronal apoptotic cell death in the retina of tamoxifen treated mice

Genotype
MGI:4838161

cn77

• Allelic Composition: Ccn2^tm2Mae/Ccn2⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

normal phenotype

no abnormal phenotype detected ( J:165111 )

• tamoxifen induced cre expression has no effect on phenotype up to 3 months after treatment

Genotype
MGI:4430543

cn78

• Allelic Composition: Sav1^tm1.1Rjo/Sav1^tm1.1Rjo; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * CD-1 * SJL

neoplasm

increased liver tumor incidence ( J:156531 )

• by 14 months of age

liver/biliary system

increased liver tumor incidence ( J:156531 )

• by 14 months of age

Genotype
MGI:5142305

cn79

• Allelic Composition: Mdm4^tm3Glo/Mdm4^tm3.1Glo; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N

normal phenotype

no abnormal phenotype detected ( J:174368 )

• tamoxifen treated adult mice are viable, do not appear sick, and do not display increased sensitivity to ionizing radiation

Genotype
MGI:3795942

cn80

• Allelic Composition: Hdac3^tm1Swh/Hdac3^tm1.1Swh; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N

cellular

abnormal cell cycle ( J:134665 )

• impaired cell cycle progression prior to metaphase in tamoxifen treated MEFs

increased fibroblast apoptosis ( J:134665 )

• in MEFs following tamoxifen treatment

abnormal DNA repair ( J:134665 )

• several markers of DNA damage are increased in MEFs after tamoxifen treatment

homeostasis/metabolism

abnormal DNA repair ( J:134665 )

• several markers of DNA damage are increased in MEFs after tamoxifen treatment

Genotype
MGI:6383666

cn81

• Allelic Composition: Ift20^tm1.1Gjp/Ift20^tm1.2Gjp; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * CBA

nervous system

abnormal photoreceptor inner segment morphology ( J:183002 )

• mice treated with tamoxifen at 4 weeks of age show rhodopsin in the inner segment, cell body, and the synapse and accumulation of rhodopsin at the Golgi complex, indicating defective opsin trafficking

vision/eye

abnormal photoreceptor inner segment morphology ( J:183002 )

• mice treated with tamoxifen at 4 weeks of age show rhodopsin in the inner segment, cell body, and the synapse and accumulation of rhodopsin at the Golgi complex, indicating defective opsin trafficking

Genotype
MGI:3620012

cn82

• Allelic Composition: Myog^tm3Whk/Myog^tm3Whk; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

mortality/aging

postnatal lethality, incomplete penetrance ( J:105925 )

• 50% of the animals die before postnatal day 10

growth/size/body

decreased body size ( J:105925 )

• surviving homozygotes are noticeably smaller than controls (homozygous floxed littermates not carrying the Cre transgene) with normal myogenin expression

decreased body weight ( J:105925 )

• at 12 weeks postnatal, homozygous null animals weigh 30% less than controls; at 6 weeks of age, null mice weighed 17.5 g compared to 20 g for controls

muscle

thin diaphragm muscle ( J:105925 )

• in one pair of homozygous littermates, diaphragms were notably thinner than those of controls but the animals breathed normally

Genotype
MGI:6404152

cn83

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

digestive/alimentary system

abnormal gastric gland morphology ( J:163367 )

• antral and pyloric hyperplasia and distended antral-pyloric region in tamoxifen-treated mice

abnormal pyloric gastric gland morphology ( J:163367 )

• hyperplasia in tamoxifen-treated mice

abnormal stomach epithelium morphology ( J:163367 )

• foveolar hyperplasia in tamoxifen-treated mice

gastric polyps ( J:163367 )

• in tamoxifen-treated mice

stomach inflammation ( J:163367 )

• acute and chronic in antral polyps of tamoxifen-treated mice

endocrine/exocrine glands

abnormal gastric gland morphology ( J:163367 )

• antral and pyloric hyperplasia and distended antral-pyloric region in tamoxifen-treated mice

abnormal pyloric gastric gland morphology ( J:163367 )

• hyperplasia in tamoxifen-treated mice

abnormal submucosal gland morphology ( J:163367 )

• hyperplastic in tamoxifen-treated mice

immune system

stomach inflammation ( J:163367 )

• acute and chronic in antral polyps of tamoxifen-treated mice

integument

alopecia ( J:163367 )

• in tamoxifen-treated mice

Genotype
MGI:3809305

cn84

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

limbs/digits/tail

abnormal limb development ( J:139257 )

• at E14 to E16, tamoxifen treated mice exhibit increased cellular senescence in developing limbs compared to in wild-type mice

Genotype
MGI:4453459

cn85

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm3Bld; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

immune system

abnormal lymphatic vessel morphology ( J:159824 )

• at E13.5 and E18.5, mice treated with tamoxifen at E11.5 and E12.5 lack identifiable mesenteric lymphatic vessels unlike in wild-type mice

• however, normal lymphatic vessel development occurs when mice are treated with tamoxifen at E14.5

abnormal lymphangiogenesis ( J:159824 )

• at E13.5 and E18.5, mice treated with tamoxifen at E11.5 and E12.5 lack identifiable mesenteric lymphatic vessels unlike in wild-type mice

• however, normal lymphatic vessel development occurs when mice are treated with tamoxifen at E14.5

Genotype
MGI:4818573

cn86

• Allelic Composition: Lmx1b^tm1Rjo/Lmx1b^tm4.1Rjo; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

vision/eye

abnormal cornea morphology ( J:161793 )

• sparsely distributed corneal keratocytes, disorganized collagen fibrils, and wavy lamellae by 4 weeks after tamoxifen treatment

corneal vascularization ( J:161793 )

• by 4 weeks after tamoxifen treatment

decreased corneal epithelium thickness ( J:161793 )

• thinner by 4 weeks after tamoxifen treatment

corneal opacity ( J:161793 )

• corneas become cloudy by 4 weeks after tamoxifen treatment

renal/urinary system

dilated renal tubule ( J:161793 )

• dilated tubules filled with eosinophilic material are seen after tamoxifen treatment

kidney degeneration ( J:161793 )

• a severe degenerative phenotype with dilated tubules filled with eosinophilic material develops after tamoxifen treatment

kidney failure ( J:161793 )

• develops after tamoxifen treatment

behavior/neurological

lethargy ( J:161793 )

• develops several weeks after tamoxifen treatment

cardiovascular system

corneal vascularization ( J:161793 )

• by 4 weeks after tamoxifen treatment

Genotype
MGI:4941477

cn87

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

skeleton

skeleton phenotype ( J:169133 )

N • tamoxifen-treated mice exhibit normal sclerotome formation

Genotype
MGI:5000506

cn88

• Allelic Composition: Trp53^tm1Glo/Trp53^tm4Glo; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

mortality/aging

extended life span ( J:171821 )

• tamoxifen-treated mice survive longer than Trp53^tm1Glo/Trp53^tm4Glo mice

neoplasm

abnormal tumor pathology ( J:171821 )

• tamoxifen-treated lymphomas exhibit decreased apoptosis response compared with tumors from Trp53^tm3.1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc mice

• tamoxifen-treated tumors exhibit decreased cell proliferation compared with control samples

• angiosarcomas treated with tamoxifen exhibit increased senescence compared with tamoxifen-treated angiosarcomas from Trp53^tm3.1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc mice

• tamoxifen-treatment induces apoptosis and senescence in giant-cell sarcoma

tumor regression ( J:171821 )

• in tamoxifen-treated mice

Genotype
MGI:5000509

cn89

• Allelic Composition: Trp53^tm3.1Glo/Trp53^tm4Glo; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

mortality/aging

extended life span ( J:171821 )

• tamoxifen-treated mice survive longer than Trp53^tm3.1Glo/Trp53^tm4Glo mice

neoplasm

abnormal tumor pathology ( J:171821 )

• tamoxifen-treated lymphomas exhibit increased apoptosis response compared with tumors from Trp53^tm1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc mice

• 3 of 5 tamoxifen-treated lymphomas exhibit senescence unlike in tumors from Trp53^tm1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc mice

• tamoxifen-treated angiosarcomas and lymphomas exhibit senescence

decreased tumor growth/size ( J:171821 )

• tamoxifen-treated mice exhibit little to no tumor growth unlike in control mice

Genotype
MGI:3711528

cn90

• Allelic Composition: Mstn^tm1Swel/Mstn^tm1Swel; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129S7/SvEvBrd-Hprt1 * C57BL/6 * CBA

muscle

increased skeletal muscle fiber diameter ( J:121233 )

• the mean cross-sectional area of an individual quadriceps fibers in tamoxifen treated mice is 42% greater than in treated controls

increased skeletal muscle mass ( J:121233 )

• after 3 months of tamoxifen treatment muscle mass is increased by 25% compared to untreated mice and treated wild-type mice in the gastrocnemius and quadriceps of males and females

Genotype
MGI:4820814

cn91

• Allelic Composition: Ret^tm2(RET)Heno/Ret^tm2(RET)Jmi; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S/Sv * C57BL/6 * CBA

digestive/alimentary system

abnormal large intestine morphology ( J:135153 )

• oligoganglionic gut, puncta of nerve fiber and cell body staining are frequently observed in the interganglionic spaces with incomplete penetrance

embryo

decreased neural crest cell number ( J:135153 )

nervous system

decreased neural crest cell number ( J:135153 )

Genotype
MGI:4820805

cn92

• Allelic Composition: Ret^tm2(RET)Heno/Ret^tm1Cos; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S/Sv * C57BL/6 * CBA

nervous system

abnormal enteric ganglia morphology ( J:135153 )

• at E15.5 a nearly complete elimination of the enteric ganglia in the colon when treated with 4-OHT

Genotype
MGI:3848824

cn93

• Allelic Composition: Plxnd1^tm1.1Tmj/Plxnd1^tm1.1Tmj; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * CBA

cardiovascular system

abnormal retina vasculature morphology ( J:143763 )

• tamoxifen-treated retinas exhibit reduced angiogenesis and hemorrhages compared to in wild-type mice

decreased angiogenesis ( J:143763 )

• tamoxifen-treated retinas exhibit reduced angiogenesis compared to in wild-type mice

abnormal vascular endothelial cell migration ( J:143763 )

• vascular invasion of tamoxifen-treated endothelial cells into matrigel plugs treated with endothelial cell growth factor is deficient compared to that of wild-type cells

hemorrhage ( J:143763 )

• tamoxifen-treated retinas exhibit hemorrhages unlike wild-type retinas

vision/eye

abnormal retina vasculature morphology ( J:143763 )

• tamoxifen-treated retinas exhibit reduced angiogenesis and hemorrhages compared to in wild-type mice

cellular

abnormal vascular endothelial cell migration ( J:143763 )

• vascular invasion of tamoxifen-treated endothelial cells into matrigel plugs treated with endothelial cell growth factor is deficient compared to that of wild-type cells

Genotype
MGI:5693885

cn94

• Allelic Composition: Tbp^tm1Xjl/Tbp⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CBA

behavior/neurological

impaired balance ( J:213011 )

• mice injected with tamoxifen at 14 months of age, but not at 3 months, take longer to walk through a balance beam

impaired coordination ( J:213011 )

• mice injected with tamoxifen show worse rotarod performance; older mice injected with tamoxifen stay on the rod for a shorter time than younger mice injected with tamoxifen

abnormal gait ( J:213011 )

• mice injected with tamoxifen exhibit abnormal gait which is most pronounced in mice that are injected at 14 months of age

short stride length ( J:213011 )

• mice injected with tamoxifen exhibit a decrease in stride length

growth/size/body

decreased body weight ( J:213011 )

• mice injected with tamoxifen for 5 days exhibit reduced body weight

• mice injected with tamoxifen at older ages (14 months) show earlier weight loss and lose more weight than those injected at younger ages (3 and 9 months)

mortality/aging

premature death ( J:213011 )

• some 14 month old mice die starting from 40 days after tamoxifen injection, however, none of the 3 month old mice die within 3 months after injection

nervous system

Purkinje cell degeneration ( J:213011 )

• mice injected with tamoxifen at 14 months of age show severe Purkinje neuron loss after 2 months of injection, while mice injected at 9 months show a modest level of degeneration, and mice injected at 3 months of age show largely intact Purkinje neurons

abnormal Purkinje cell dendrite morphology ( J:213011 )

• dendritic branches are decreased in mice injected with tamoxifen at 14 months of age

thin cerebellar molecular layer ( J:213011 )

• molecular layer thickness is decreased in mice injected with tamoxifen at 14 months of age

skeleton

kyphosis ( J:213011 )

• hunch-back appearance of 3, 9, and 14 month old mice is seen at 130, 75, and 50 days after tamoxifen injection

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spinocerebellar ataxia type 17		DOID:0050967	OMIM:607136	J:213011

Genotype
MGI:5435674

cn95

• Allelic Composition: Fktn^tm1Kcam/Fktn^tm1Kcam; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CBA

muscle

dystrophic muscle ( J:187144 )

• iliopsoas muscle from mice treated with tamoxifen show indications of dystrophic disease

• variations in fiber size

• necrosis

• increase in centrally nucleated fibers

homeostasis/metabolism

increased circulating creatine kinase level ( J:187144 )

• levels begin to rise at 14 weeks of age and are significantly elevated at 16-20 weeks after tamoxifen treatment at 10 weeks of age

growth/size/body

growth/size/body region phenotype ( J:187144 )

N • normal body weight at 4- 20 weeks of age after tamoxifen treatment

behavior/neurological

behavior/neurological phenotype ( J:187144 )

N • normal forelimb grip strength at 4-20 weeks of age after tampxifen treatment

N • normal open field activity at 4-20 weeks of age after tampxifen treatment

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

Genotype
MGI:3838797

cn96

• Allelic Composition: Pou4f2^tm4(DTA)Whk/Pou4f2⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CBA

vision/eye

abnormal optic nerve morphology ( J:146558 )

• reduced cross-sectional area by 48.8% in 3 months after a 5 day course of tamoxifen treatment

• cross-sectional area reduced to 19.7% of controls at ten months after a 5 day course of tamoxifen treatment

• axons disorganized

optic nerve degeneration ( J:146558 )

• progressive degeneration over the course of ten months after a 5 day course of tamoxifen treatment

• severe axon degeneration and vacuolation

• empty or abnormal myelin sheaths

optic nerve atrophy ( J:146558 )

thin retina ganglion layer ( J:146558 )

• 60% reduction in the number of cells of the ganglion layer one month after a 5 day course of tamoxifen treatment

abnormal vision ( J:146558 )

• 33% of time spent in the light as opposed to 6% for controls after 1-2 hours of dark adaptation

nervous system

gliosis ( J:146558 )

• reactive gliosis triggered one month after a 5 day course of tamoxifen treatment

abnormal optic nerve morphology ( J:146558 )

• reduced cross-sectional area by 48.8% in 3 months after a 5 day course of tamoxifen treatment

• cross-sectional area reduced to 19.7% of controls at ten months after a 5 day course of tamoxifen treatment

• axons disorganized

optic nerve degeneration ( J:146558 )

• progressive degeneration over the course of ten months after a 5 day course of tamoxifen treatment

• severe axon degeneration and vacuolation

• empty or abnormal myelin sheaths

optic nerve atrophy ( J:146558 )

Genotype
MGI:4453351

cn97

• Allelic Composition: Tg(CAG-Bgeo/Lhx2,-GFP)#Lcar/0; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * CBA

integument

abnormal hair cycle ( J:159209 )

• areas of skin that are tamoxifen treated prematurely initiated anagen and are in anagen at 9 weeks of age, whereas in wild-type mice and untreated areas of skin are in telogen.

Genotype
MGI:6467551

cn98

• Allelic Composition: Rab35^tm1.1Vha/Rab35^tm1.1Vha; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129/Sv * 129S4/SvJaeSor * C57BL/6J * C57BL/6 * CBA

nervous system

increased astrocyte size ( J:294178 )

• larger in vitro cultured astrocytes after tamoxifen induction

Genotype
MGI:3850050

cn99

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

immune system

abnormal macrophage physiology ( J:150054 )

• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro

abnormal dendritic cell physiology ( J:150054 )

• bone marrow derived dendritic cells hypersecrete the mature form of IL-1beta in response to activation

• the maximal response is 300-fold greater than controls

• DCs are able to secrete IL1-beta without the presence of exogenous ATP

abnormal dendritic cell antigen presentation ( J:150054 )

• mutant DCs cells have an enhanced ability to stimulate T cells to differentiate into a Th17 subtypes when presenting cognate antigen

• mutant DCs also enhance Th1 and Th2 differentation when co-cultured with T cells in the presence of polarizing cytokines

hematopoietic system

abnormal macrophage physiology ( J:150054 )

• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro

Genotype
MGI:3850052

cn100

• Allelic Composition: Nlrp3^tm2Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

immune system

abnormal macrophage physiology ( J:150054 )

• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro

abnormal dendritic cell physiology ( J:150054 )

• bone marrow derived dendritic cells (DCs) spontaneously secrete high levels of IL1-beta in response to cold (32 degrees) incubation

• DCs also hypersecrete the mature form of IL-1beta in response to activation

• the maximal response is 150-fold greater than controls

• DCs are able to secrete IL1-beta without the presence of exogenous ATP

hematopoietic system

abnormal macrophage physiology ( J:150054 )

• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial cold autoinflammatory syndrome 1		DOID:0090062	OMIM:120100	J:150054

Genotype
MGI:3758925

cn101

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/?; Thra^tm1Ffla/Thra⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

nervous system

abnormal cerebellum morphology ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

growth/size/body

abnormal postnatal growth ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

cardiovascular system

abnormal heart rate ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

skeleton

delayed bone ossification ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

Genotype
MGI:4454657

cn102

• Allelic Composition: Foxn1^tm1.1Dmsu/Foxn1^tm1.1Dmsu; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA * SJL

Thymic atrophy in tamoxifen treated Foxn1^tm1.1Dmsu/Foxn1^tm1.1Dmsu Tg(KRT5-cre/ERT2)2Ipc/0 mice and Foxn1^tm1.1Dmsu/Foxn1^tm1.1Dmsu Tg(CAG-cre/Esr1*)5Amc/0 mice

immune system

abnormal thymus morphology ( J:159773 )

• following tamoxifen treatment, mice exhibit a decrease in thymic stromal cells compared to in wild-type mice

small thymus ( J:159773 )

• following tamoxifen treatment

thymus atrophy ( J:159773 )

• following tamoxifen treatment

decreased thymocyte number ( J:159773 )

• following tamoxifen treatment

decreased double-positive T cell number ( J:159773 )

• following tamoxifen treatment

hematopoietic system

abnormal thymus morphology ( J:159773 )

• following tamoxifen treatment, mice exhibit a decrease in thymic stromal cells compared to in wild-type mice

small thymus ( J:159773 )

• following tamoxifen treatment

thymus atrophy ( J:159773 )

• following tamoxifen treatment

decreased thymocyte number ( J:159773 )

• following tamoxifen treatment

decreased double-positive T cell number ( J:159773 )

• following tamoxifen treatment

endocrine/exocrine glands

abnormal thymus morphology ( J:159773 )

• following tamoxifen treatment, mice exhibit a decrease in thymic stromal cells compared to in wild-type mice

small thymus ( J:159773 )

• following tamoxifen treatment

thymus atrophy ( J:159773 )

• following tamoxifen treatment

decreased thymocyte number ( J:159773 )

• following tamoxifen treatment

Genotype
MGI:4454658

cn103

• Allelic Composition: Foxn1^nu/Foxn1^tm1.1Dmsu; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA * SJL

immune system

increased thymocyte apoptosis ( J:159773 )

• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice

abnormal thymus epithelium morphology ( J:159773 )

• following tamoxifen treatment, medullary thymic epithelial cells are reduced compared to in wild-type mice

• mature medullary thymic epithelial cells are more affected than presumptive medullary thymic epithelial cell precursors following tamoxifen treatment

• however, cortical thymic epithelial cells are not significantly reduced following tamoxifen treatment

decreased thymocyte number ( J:159773 )

• following tamoxifen treatment

hematopoietic system

increased thymocyte apoptosis ( J:159773 )

• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice

abnormal thymus epithelium morphology ( J:159773 )

• following tamoxifen treatment, medullary thymic epithelial cells are reduced compared to in wild-type mice

• mature medullary thymic epithelial cells are more affected than presumptive medullary thymic epithelial cell precursors following tamoxifen treatment

• however, cortical thymic epithelial cells are not significantly reduced following tamoxifen treatment

decreased thymocyte number ( J:159773 )

• following tamoxifen treatment

cellular

increased thymocyte apoptosis ( J:159773 )

• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice

endocrine/exocrine glands

increased thymocyte apoptosis ( J:159773 )

• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice

abnormal thymus epithelium morphology ( J:159773 )

• following tamoxifen treatment, medullary thymic epithelial cells are reduced compared to in wild-type mice

• mature medullary thymic epithelial cells are more affected than presumptive medullary thymic epithelial cell precursors following tamoxifen treatment

• however, cortical thymic epithelial cells are not significantly reduced following tamoxifen treatment

decreased thymocyte number ( J:159773 )

• following tamoxifen treatment

Genotype
MGI:3715267

cn104

• Allelic Composition: Gfra1^tm1Jmi/Gfra1^tm2Jmi; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA * SJL

nervous system

nervous system phenotype ( J:122607 )

N • with 4-OHT treatment on E13.5 rather than E15.5, complete loss of enteric neurons in colon is still observed at E18.5, but no abnormalities in enteric ganglia of small intestine is seen

abnormal neuronal precursor proliferation ( J:122607 )

• fewer ENS progenitors are proliferating in the midgut at E13.5 in embryos treated with 4-OHT at E11.5 (12.2% vs 24% in controls)

abnormal enteric nervous system morphology ( J:122607 )

abnormal enteric ganglia morphology ( J:122607 )

• at E18.5, ganglion structure and innervation in the colon is completely disrupted relative to control mice with 4-OHT treatement at E15.5

• enteric ganglion cells die within 36 hours after 4-OHT treatment

absent enteric neurons ( J:122607 )

• with 4-OHT treatment on E15.5, enteric ganglia and neurons are lost in the colon by birth

abnormal nervous system development ( J:122607 )

• abnormal thick nerve bundles are observed in the colons of E18.5 embryos after 4-hydroxytamoxifen, 4-OHT treatment on E15.5; this are likely un-defasciculated extrinsic nerve fibers

cellular

abnormal cell nucleus morphology ( J:122607 )

• nuclei of dying ganglion cells in mutants display numerous indentations in nuclear membrane, some with abnormal constriction of the nuclear membrane resulting in multilobation of the nuclei

• cells are shrunken with condensation of marginal heterochromatin and chromatin masses dispersed in the karyoplasms; diminuition of the cytoplasm and heterochromatin condensation in the nuclei are enhanced in ganglion cells in the myenteric layer

abnormal cell death ( J:122607 )

• enteric ganglion cells die within 36 hours of Gfra1 inactivation induced by 4-OHT treatment of pregnant females, but cell death is by mechanism other than apoptosis; enteric neuron death is not dependent on caspases or Bax

• some cells contain autolysosomes; almost no autophagosomes are detected in mutants at any stage of cell death

abnormal neuronal precursor proliferation ( J:122607 )

• fewer ENS progenitors are proliferating in the midgut at E13.5 in embryos treated with 4-OHT at E11.5 (12.2% vs 24% in controls)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hirschsprung's disease		DOID:10487	OMIM:600156 OMIM:606874 OMIM:606875 OMIM:608462 OMIM:611644	J:122607

Genotype
MGI:6154270

cn105

• Allelic Composition: Trip11^tm1.1Psmi/Trip11^tm1.2Psmi; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/?; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL/J

cellular

abnormal Golgi vesicle transport ( J:253969 )

• primary chondrocyte cultures treated with tamoxifen to inactivate the loxP-flanked allele have a change in the protein profile in the proteomes with many of the proteins with altered expression playing a role in membrane trafficking or Golgi/endoplasmic reticulum function, so while chondrocyte secretion continues to function the specific set of secreted proteins differs

Genotype
MGI:6382630

cn106

• Allelic Composition: Tmem30a^tm1.1Xjz/Tmem30a^tm1.1Xjz; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129/SvEv * C57BL/6 * CBA

vision/eye

decreased retina ganglion cell number ( J:253580 )

• at age P27 after tamoxifen administration at P20

• normal at age P25 after tamoxifen administration at P20

absent photoreceptor outer segment ( J:253580 )

• absent OS at age P30 after tamoxifen administration at P20

• present at age P25 after tamoxifen administration at P20

short photoreceptor outer segment ( J:253580 )

• at age P27 after tamoxifen administration at P20

• normal at age P25 after tamoxifen administration at P20

photoreceptor outer segment degeneration ( J:253580 )

• normal at age P25 after tamoxifen administration at P20

• absent OS at age P30 after tamoxifen administration at P20

thin retina outer nuclear layer ( J:253580 )

• 50% reduction in thickness at age P27 after tamoxifen administration at P20

• 2-3 cells per row (compared to 10-11) at age P30 after tamoxifen administration at P20

• normal at age P25 after tamoxifen administration at P20

abnormal cone electrophysiology ( J:253580 )

• 50% reduction in a-wave amplitude with scotopic ERG at age P27 after tamoxifen administration at P20

• 40% reduction in b-wave amplitude with scotopic ERG at age P27 after tamoxifen administration at P20

• normal scotopic ERG at age P25 after tamoxifen administration at P20

nervous system

decreased retina ganglion cell number ( J:253580 )

• at age P27 after tamoxifen administration at P20

• normal at age P25 after tamoxifen administration at P20

absent photoreceptor outer segment ( J:253580 )

• absent OS at age P30 after tamoxifen administration at P20

• present at age P25 after tamoxifen administration at P20

short photoreceptor outer segment ( J:253580 )

• at age P27 after tamoxifen administration at P20

• normal at age P25 after tamoxifen administration at P20

photoreceptor outer segment degeneration ( J:253580 )

• normal at age P25 after tamoxifen administration at P20

• absent OS at age P30 after tamoxifen administration at P20

Genotype
MGI:6724166

cn107

• Allelic Composition: Epas1^tm1Mcs/Epas1^tm1.1Mcs; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

cardiovascular system

cardiovascular system phenotype ( J:302384 )

N • tamoxifen-treated mice exhibit normal carotid body morphology

heart left ventricle hypertrophy ( J:302384 )

• likely secondary to anemia in tamoxifen-treated

abnormal type I cell of carotid body physiology ( J:302384 )

• impaired responsiveness to hypoxia with reduced secretory rate in tamoxifen-treated mice

• lower shifted quantal charge and reduced mean charge per event in tamoxifen-treated mice exposed to mild stimuli

• reduced increase in NADH and mitochondrial function induced by hypoxia in tamoxifen-treated mice

• however, tamoxifen-treated mice exhibit normal hypercapnia and depolarization with high extracellular potassium ion, and normal secretion induced by CO2 and high potassium ion

hematopoietic system

anemia ( J:302384 )

• in tamoxifen-treated mice

decreased hematocrit ( J:302384 )

• in tamoxifen-treated mice

homeostasis/metabolism

abnormal physiological response to hypoxia ( J:302384 )

• decreased hypoxic ventilatory response in tamoxifen-treated mice exposed to hypoxic conditions

• however, response to hypercapnia is normal and tamoxifen-treated mice exhibit a small transient hyperventilatory response at the onset of exposure to hypoxia

growth/size/body

heart left ventricle hypertrophy ( J:302384 )

• likely secondary to anemia in tamoxifen-treated

muscle

heart left ventricle hypertrophy ( J:302384 )

• likely secondary to anemia in tamoxifen-treated

nervous system

abnormal type I cell of carotid body physiology ( J:302384 )

• impaired responsiveness to hypoxia with reduced secretory rate in tamoxifen-treated mice

• lower shifted quantal charge and reduced mean charge per event in tamoxifen-treated mice exposed to mild stimuli

• reduced increase in NADH and mitochondrial function induced by hypoxia in tamoxifen-treated mice

• however, tamoxifen-treated mice exhibit normal hypercapnia and depolarization with high extracellular potassium ion, and normal secretion induced by CO2 and high potassium ion

Genotype
MGI:4459062

cn108

• Allelic Composition: Bax^tm1Sjk/Bax^tm1Sjk; Ret^tm1Heno/Ret^{tm3.1(Bcl2l1)Heno}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

nervous system

abnormal enteric neuron morphology ( J:159854 )

• tamoxifen-treated mice exhibit loss of enteric neurons unlike similarly treated control mice (Ret^tm1Heno/Ret⁺ Tg(CAG-cre/Esr1*)5Amc mice)

Genotype
MGI:4459061

cn109

• Allelic Composition: Ret^tm1Heno/Ret^{tm3.1(Bcl2l1)Heno}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

digestive/alimentary system

abnormal defecation ( J:159854 )

• tamoxifen-treated mice exhibit decreased stool frequency compared with control mice

• 2 to 5 tamoxifen-treated mice exhibit hard feces that accumulates in the distal colon unlike in control mice

abnormal feces composition ( J:159854 )

• tamoxifen-treated mice exhibit wet stool weight and water stool content compared with control mice

growth/size/body

decreased body weight ( J:159854 )

• in tamoxifen-treated mice

nervous system

abnormal enteric neuron morphology ( J:159854 )

• 40% of tamoxifen-treated mice exhibit reduced enteric neurons compared with similarly treated control mice (Ret^tm1Heno/Ret⁺ Tg(CAG-cre/Esr1*)5Amc mice)

• tamoxifen-treated mice exhibit fewer NOS-expressing neurons compared to in control mice

• however, 60% of tamoxifen-treated mice exhibit normal enteric nervous system development

Genotype
MGI:4459060

cn110

• Allelic Composition: Ret^tm1Heno/Ret^tm2(RET)Heno; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

nervous system

abnormal enteric neuron morphology ( J:159854 )

• tamoxifen-treated mice exhibit fewer enteric neurons than in similarly controls (Ret^tm1Heno/Ret⁺ Tg(CAG-cre/Esr1*)5Amc mice)

Genotype
MGI:3716204

cn111

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Smo/EYFP)Amc}/?; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:114992 )

• following tamoxifen treatment, all mice are dead by 18 weeks of observation unlike untreated mice and Ptch1^tm1Mps heterozygotes

neoplasm

increased basal cell carcinoma incidence ( J:114992 )

• following tamoxifen treatment, mice exhibit macroscopic basal cell carcinomas (BBC) where as all other mice develop BBC tumors at 8 weeks

increased rhabdomyosarcoma incidence ( J:114992 )

• present without tamoxifen treatment (average number 3)

• following tamoxifen treatment, the multiplicity of tumors is increased (average number 7)

• mostly confined to rear thigh and abdominal wall

• following tamoxifen treatment, tumors are detected in skeletal muscle of the head, neck, tongue and paratesticular regions

• following tamoxifen treatment at P10, age of onset is accelerated to week 5 compared to week 9 in untreated mice

increased medulloblastoma incidence ( J:114992 )

• found in 27% of mice and 40% of mice following tamoxifen treatment

digestive/alimentary system

intestine polyps ( J:114992 )

• diverticular harmatomatous lesions in the intestine occur at a higher rate following treatment with tamoxifen (20% without treatment and 80% following treatment)

gastric polyps ( J:114992 )

• diverticular harmatomatous lesions in the stomach occur at a higher rate following treatment with tamoxifen (less than 5% of mice after treatment)

endocrine/exocrine glands

abnormal pancreas morphology ( J:114992 )

• cystic metaplastic lesions are observed with increased frequency following tamoxifen treatment

integument

increased basal cell carcinoma incidence ( J:114992 )

• following tamoxifen treatment, mice exhibit macroscopic basal cell carcinomas (BBC) where as all other mice develop BBC tumors at 8 weeks

nervous system

increased medulloblastoma incidence ( J:114992 )

• found in 27% of mice and 40% of mice following tamoxifen treatment

muscle

increased rhabdomyosarcoma incidence ( J:114992 )

• present without tamoxifen treatment (average number 3)

• following tamoxifen treatment, the multiplicity of tumors is increased (average number 7)

• mostly confined to rear thigh and abdominal wall

• following tamoxifen treatment, tumors are detected in skeletal muscle of the head, neck, tongue and paratesticular regions

• following tamoxifen treatment at P10, age of onset is accelerated to week 5 compared to week 9 in untreated mice

Genotype
MGI:5428000

cn112

• Allelic Composition: Wnt9b^tm1.1Amc/Wnt9b^tm1.2Amc; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:151498 )

• all mice treated with tamoxifen from E15.5 die by P90

renal/urinary system

kidney cyst ( J:151498 )

• in mice treated with tamoxifen from E15.5 to P10

• however, mice treated with tamoxifen after P10 do not develop cysts

growth/size/body

kidney cyst ( J:151498 )

• in mice treated with tamoxifen from E15.5 to P10

• however, mice treated with tamoxifen after P10 do not develop cysts

Genotype
MGI:4888376

cn113

• Allelic Composition: Cxcl12^tm1.1Ystz/Cxcl12^tm1.2Ystz; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA * FVB/N

hematopoietic system

decreased pro-B cell number ( J:168434 )

• in the bone marrow of tamoxifen-treated mice

increased neutrophil cell number ( J:168434 )

• tamoxifen-treated mice exhibit an increase in the percentage of circulating neutrophils compared with wild-type mice

decreased hematopoietic stem cell number ( J:168434 )

• tamoxifen-treated mice exhibit a reduction in long term hematopoietic stem cells compared with wild-type mice

increased hematopoietic stem cell number ( J:168434 )

• tamoxifen-treated mice exhibit an increase in LSK cells in the bone marrow and peripheral blood compared with wild-type mice

• tamoxifen-treated mice exhibit a 5-fold and 15-fold increase in LSK cells and colony-forming unit cells, respectively, in the spleen compared with wild-type mice

• tamoxifen-treated mice exhibit an increased in hematopoietic progenitors compared with wild-type mice

abnormal hematopoietic system physiology ( J:168434 )

• in a 5-fluorouracil myelosuppression model, tamoxifen-treated mice exhibit increased survival and faster hematologic recovery with less obvious bone marrow regeneration along the endosteal surface and ectopic regeneration in the perisinusoidal space compared with wild-type mice

abnormal hematopoietic stem cell physiology ( J:168434 )

• tamoxifen-treated mice exhibit hyperproliferation and reduced quiescence of hematopoietic stem/progenitor cells compared with wild-type mice

immune system

decreased pro-B cell number ( J:168434 )

• in the bone marrow of tamoxifen-treated mice

increased neutrophil cell number ( J:168434 )

• tamoxifen-treated mice exhibit an increase in the percentage of circulating neutrophils compared with wild-type mice

Genotype
MGI:5426706

cn114

• Allelic Composition: Nr1d1^tm1.1Rev/Nr1d1^tm1.1Rev; Nr1d2^tm1.1Rev/Nr1d2^tm1.1Rev; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: BALB/cJ * C57BL/6 * C57BL/6J * CBA

homeostasis/metabolism

decreased circulating glucose level ( J:183855 )

• in tamoxifen-treated mice

increased circulating free fatty acids level ( J:183855 )

• in tamoxifen-treated mice

decreased circulating triglyceride level ( J:183855 )

• in tamoxifen-treated mice

decreased respiratory quotient ( J:183855 )

• in tamoxifen-treated mice

behavior/neurological

shortened circadian behavior period ( J:183855 )

• shortened and fragmented activity period in tamoxifen-treated mice

Genotype
MGI:5014087

cn115

• Allelic Composition: Pml^{tm1(PML/RARA)Ley}/Pml⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: BALB/cJ * C57BL/6 * CBA

hematopoietic system

enlarged spleen ( J:172024 )

• in one tamoxifen-treated mouse

decreased hematopoietic stem cell number ( J:172024 )

• small decrease in tamoxifen-treated mice

abnormal hematopoietic stem cell physiology ( J:172024 )

• hematopoietic stem cells from tamoxifen-treated mice exhibit in vitro self-renewal compared with control cells

• however, tamoxifen-treated mice do not exhibit myeloproliferative disease

immune system

enlarged spleen ( J:172024 )

• in one tamoxifen-treated mouse

growth/size/body

enlarged spleen ( J:172024 )

• in one tamoxifen-treated mouse

Genotype
MGI:5607142

cn116

• Allelic Composition: Pou4f1^tm1.1Gan/Pou4f1^tm1.1Gan; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA

vision/eye

vision/eye phenotype ( J:215207 )

N • mice treated with tamoxifen exhibit normal retinal interneurons and Muller glial cells and normal survival of adult retinal ganglion cells

Genotype
MGI:5607145

cn117

• Allelic Composition: Pou4f2^tm2.1Gan/Pou4f2^tm2.1Gan; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA

vision/eye

vision/eye phenotype ( J:215207 )

N • mice treated with tamoxifen exhibit normal retinal interneurons and Muller glial cells and normal survival of adult retinal ganglion cells

Genotype
MGI:5013602

cn118

• Allelic Composition: Cop1^tm1.1Vmd/Cop1^tm2.1Vmd; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * CBA

reproductive system

abnormal prostate gland physiology ( J:172653 )

♂ • xenografted prostate epithelium cells exhibit increased proliferation and form neoplastic prostate structures compared with xenografted wild-type cells

endocrine/exocrine glands

abnormal prostate gland physiology ( J:172653 )

♂ • xenografted prostate epithelium cells exhibit increased proliferation and form neoplastic prostate structures compared with xenografted wild-type cells

Genotype
MGI:5581523

cn119

• Allelic Composition: Sel1l^{tm1c(KOMP)Wtsi}/Sel1l^{tm1c(KOMP)Wtsi}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * CBA * SJL
• Cell Lines: EPD0284_3_D08

Exocrine pancreatic insufficiency in Sel1l^{tm1c(KOMP)Wtsi}/Sel1l^{tm1c(KOMP)Wtsi} Tg(CAG-cre/Esr1*)5Amc/0 mice

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:206568 )

• death within 2-3 weeks after a 3 day series of tamoxifen injections

moribund ( J:206568 )

• mice treated with tamoxifen become moribund

homeostasis/metabolism

abnormal intestinal lipid absorption ( J:206568 )

• treated mice fail to properly absorb lipids

steatorrhea ( J:206568 )

decreased body temperature ( J:206568 )

• mice treated with tamoxifen develop a reduced body temperature

increased susceptibility to xenobiotic induced morbidity/mortality ( J:206568 )

• death within 2-3 weeks after a 3 day series of tamoxifen injections

growth/size/body

decreased body size ( J:206568 )

• mice treated with tamoxifen become runted

postnatal growth retardation ( J:206568 )

• mice given three injected doses of tamoxifen start to lose weight about 8 days after the start of injections

• blood glucose and energy expenditure remain normal

behavior/neurological

increased food intake ( J:206568 )

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:206568 )

• pancreas is diffusely dark red and soft at 8 days after treatment

exocrine pancreas atrophy ( J:206568 )

• weight is about 1/2 control pancreas weight

• dramatic morphological degeneration

• reduced eosinophilic secretory zymogen granules

• increased basophilia marked anisokaryosis and binucleate cells mild pancreatitis

abnormal intestinal lipid absorption ( J:206568 )

• treated mice fail to properly absorb lipids

abnormal pancreatic acinar cell physiology ( J:206568 )

• alpha amylase and lipase levels significantly reduced

• activities reduced 60-80%

steatorrhea ( J:206568 )

endocrine/exocrine glands

increased pancreas apoptosis ( J:206568 )

• 3-4 fold increase in TUNEL positive cells in the pancreas

abnormal exocrine pancreas morphology ( J:206568 )

• pancreas is diffusely dark red and soft at 8 days after treatment

exocrine pancreas atrophy ( J:206568 )

• weight is about 1/2 control pancreas weight

• dramatic morphological degeneration

• reduced eosinophilic secretory zymogen granules

• increased basophilia marked anisokaryosis and binucleate cells mild pancreatitis

abnormal pancreatic acinar cell physiology ( J:206568 )

• alpha amylase and lipase levels significantly reduced

• activities reduced 60-80%

cellular

abnormal cell morphology ( J:206568 )

• secretory zymogen granules are significantly reduced in size

• ratio of polysomes to monosomes is reduced by 50% after treatment

abnormal endoplasmic reticulum morphology ( J:206568 )

• extensively swollen and fragmented in pancreatic cells

increased cell death ( J:206568 )

• increased death of pancreatic exocrine cells by day 13 after tamoxifen injection

increased pancreas apoptosis ( J:206568 )

• 3-4 fold increase in TUNEL positive cells in the pancreas

Genotype
MGI:7616226

cn120

• Allelic Composition: Cemip2^tm1.1Cya/Cemip2^tm1.1Cya; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

skeleton

abnormal bone marrow cavity morphology ( J:317425 )

• hyaluronan deposits in the bone marrow matrix in tamoxifen treated mice

homeostasis/metabolism

increased hyaluronic acid level ( J:317425 )

• in tamoxifen treated mice tissue hyaluronan levels are increased in the liver, lung, and kidney

• prominent hyaluronan deposits in the lymph nodes

• deposits are also seen in the liver sinusoid, alveolar wall of the lung, mesangium of the kidney, the dermis, and the bone marrow matrix

increased circulating hyaluronic acid level ( J:317425 )

• rapid accumulation of hyaluronan in the blood at 12 and 19 days after tamoxifen treatment

• hyaluronan population contains a significant amount of undigested high molecular weight species

abnormal metabolism ( J:317425 )

• significant reduction of hyaluronan fragmentation in the lymph nodes and liver indicating reduced degradation in tamoxifen treated mice

integument

abnormal dermal layer morphology ( J:317425 )

• hyaluronan deposits in tamoxifen treated mice

respiratory system

abnormal pulmonary alveolus morphology ( J:317425 )

• hyaluronan deposits in tamoxifen treated mice

renal/urinary system

abnormal renal corpuscle morphology ( J:317425 )

• hyaluronan deposits in tamoxifen treated mice

cardiovascular system

abnormal liver sinusoid morphology ( J:317425 )

• hyaluronan deposits in tamoxifen treated mice

immune system

abnormal lymph node morphology ( J:317425 )

• prominent hyaluronan deposits in the lymph nodes in tamoxifen treated mice

liver/biliary system

abnormal liver sinusoid morphology ( J:317425 )

• hyaluronan deposits in tamoxifen treated mice

Genotype
MGI:3653933

cn121

• Allelic Composition: Aqp2^tm1Bxy/Aqp2^tm1Bxy; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

homeostasis/metabolism

abnormal urine osmolality ( J:110648 )

• after 18 hours of water deprivation, urine osmolality increases from 1860 to 2720 mosmol/ kg water in wild-type mice, but little increase is seen in tamoxifen-treated mutants

decreased urine osmolality ( J:110648 )

• after tamoxifen-induced deletion of Aqp2. osmolality of urine in mutants decreases from ~2000 mosmol/kg water to <500 mosmol/kg water by 4-5 days after tamoxifen injection and remains low at ~ 200 mosmol/kg water

renal/urinary system

abnormal urine osmolality ( J:110648 )

• after 18 hours of water deprivation, urine osmolality increases from 1860 to 2720 mosmol/ kg water in wild-type mice, but little increase is seen in tamoxifen-treated mutants

decreased urine osmolality ( J:110648 )

• after tamoxifen-induced deletion of Aqp2. osmolality of urine in mutants decreases from ~2000 mosmol/kg water to <500 mosmol/kg water by 4-5 days after tamoxifen injection and remains low at ~ 200 mosmol/kg water

dilated kidney collecting duct ( J:110648 )

• dilatation of collecting ducts in the renal cortex and medulla is observed in kidneys 6 weeks after induction resulting from polyuria

kidney medulla atrophy ( J:110648 )

• 6 weeks after induction, many kidneys show medullary atrophy

hydroureter ( J:110648 )

• seen in mice 6 weeks after tamoxifen induction

abnormal urinary bladder morphology ( J:110648 )

• seen in mice 6 weeks after tamoxifen induction

polyuria ( J:110648 )

• after tamoxifen treatment, mice are severely polyuric, excreting ~10-fold greater fluid than controls

Genotype
MGI:3777343

cn122

• Allelic Composition: Nr2e1^tm1Rev/Nr2e1^tm1Rev; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: C57BL/6 * CBA

nervous system

abnormal neuron differentiation ( J:132664 )

• three weeks of voluntary running results in an increased number of dividing cells in the brain

• reduced pool of neural stem cells

behavior/neurological

behavior/neurological phenotype ( J:132664 )

N • contextual fear conditioning is normal

N • tone-cued memory is normal

cellular

abnormal neuron differentiation ( J:132664 )

• three weeks of voluntary running results in an increased number of dividing cells in the brain

• reduced pool of neural stem cells

Genotype
MGI:4422186

cn123

• Allelic Composition: Stk3^tm1.1Yy/Stk3^tm1Yy; Stk4^tm1.1Yy/Stk4^tm1.1Yy; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

liver/biliary system

increased hepatocyte proliferation ( J:156541 )

enlarged liver ( J:156541 )

• at 1 - 7 months after tamoxifen treatment

increased liver tumor incidence ( J:156541 )

• some mice treated with tamoxifen at birth develop cholangiocarcinomas composed of mainly multilayered biliary epithelial cells

increased hepatocellular carcinoma incidence ( J:156541 )

• all mice treated with tamoxifen at birth develop tumors which display characteristics of hepatocellular carcinoma by 6 months of age

neoplasm

increased liver tumor incidence ( J:156541 )

• some mice treated with tamoxifen at birth develop cholangiocarcinomas composed of mainly multilayered biliary epithelial cells

increased hepatocellular carcinoma incidence ( J:156541 )

• all mice treated with tamoxifen at birth develop tumors which display characteristics of hepatocellular carcinoma by 6 months of age

increased carcinoma incidence ( J:156541 )

• some mice treated with tamoxifen at birth develop cholangiocarcinomas composed of mainly multilayered biliary epithelial cells

cardiovascular system

enlarged heart ( J:156541 )

• in some mice at 1 - 7 months after tamoxifen treatment

digestive/alimentary system

enlarged stomach ( J:156541 )

• at 1 - 7 months after tamoxifen treatment

hematopoietic system

enlarged spleen ( J:156541 )

• in some mice at 1 - 7 months after tamoxifen treatment

immune system

enlarged spleen ( J:156541 )

• in some mice at 1 - 7 months after tamoxifen treatment

cellular

increased hepatocyte proliferation ( J:156541 )

growth/size/body

enlarged heart ( J:156541 )

• in some mice at 1 - 7 months after tamoxifen treatment

enlarged liver ( J:156541 )

• at 1 - 7 months after tamoxifen treatment

enlarged spleen ( J:156541 )

• in some mice at 1 - 7 months after tamoxifen treatment

Genotype
MGI:4947714

cn124

• Allelic Composition: Kat7^tm1.1Avo/Kat7^tm1.1Avo; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

cellular

cellular phenotype ( J:170405 )

N • tamoxifen-treated cells exhibit normal cell morphology or excessive cell death

Genotype
MGI:5297907

cn125

• Allelic Composition: Map2k7^tm1Rjd/Map2k7^tm1Rjd; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

nervous system

nervous system phenotype ( J:178060 )

N • tamoxifen-treated neurons exhibit normal increases in neuron apoptosis following beta-amyloid 42 stimulation

Genotype
MGI:5297908

cn126

• Allelic Composition: Map2k4^tm1Ctr/Map2k4^tm1Ctr; Map2k7^tm1Rjd/Map2k7^tm1Rjd; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

cellular

decreased neuron apoptosis ( J:178060 )

• after beta-amyloid 42 stimulation, tamoxifen-treated neurons remain viable and do not exhibit increased caspase 3 activity unlike control neurons

nervous system

decreased neuron apoptosis ( J:178060 )

• after beta-amyloid 42 stimulation, tamoxifen-treated neurons remain viable and do not exhibit increased caspase 3 activity unlike control neurons

Genotype
MGI:5297910

cn127

• Allelic Composition: Map2k4^tm1Ctr/Map2k4^tm1Ctr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

nervous system

nervous system phenotype ( J:178060 )

N • tamoxifen-treated neurons exhibit normal increases in neuron apoptosis following beta-amyloid 42 stimulation

Genotype
MGI:5304417

cn128

• Allelic Composition: Lbx1^tm1.1Khan/Lbx1^tm1.1Khan; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

muscle

abnormal skeletal muscle morphology ( J:178868 )

• tamoxifen-treated mice lack limb extensor muscles

Genotype
MGI:5468353

cn129

• Allelic Composition: Ccnd3^tm2.1Pisc/Ccnd3^tm2.1Pisc; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

normal phenotype

no abnormal phenotype detected ( J:192032 )

• tamoxifen-treated mice exhibit no obvious abnormalities

Genotype
MGI:5490590

cn130

• Allelic Composition: Nrl^tm1Jcco/Nrl^tm1Jcco; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

Adult rods are reprogrammed into cone-like cells in Nrl^tm1Jcco/Nrl^tm1Jcco Tg(CAG-cre/Esr1*)5Amc/0 mice

vision/eye

abnormal retina photoreceptor morphology ( J:193697 )

• tamoxifen-treated mice exhibit reprogramming of rods into cone-like cells

abnormal eye physiology ( J:193697 )

• in response to a series of light stimuli, reprogrammed retina in tamoxifen-treated mice exhibit lower maximal response amplitudes compared with control mice

• photopigment-bleached reprogrammed retina from tamoxifen-treated mice allowed to dark adapt in the presence of 9-cis-retinol are able to completely recover their photoresponse and largely restore their sensitivity

abnormal rod electrophysiology ( J:193697 )

• decreased scotopic a, but not b, wave amplitude in tamoxifen-treated mice

• like cone cells, dark-adapted reprogrammed rod cells in tamoxifen-treated mice exhibit a 35-fold desensitization and more rapid inactivation of photoresponse

nervous system

abnormal retina photoreceptor morphology ( J:193697 )

• tamoxifen-treated mice exhibit reprogramming of rods into cone-like cells

Genotype
MGI:5502227

cn131

• Allelic Composition: Map3k12^tm1Lewc/Map3k12^tm1Lewc; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

nervous system

decreased retina ganglion cell number ( J:196076 )

• 6 weeks after optic nerve crush, tamoxifen-treated mice retain their ganglion cell axons and show only 13% loss of ganglion cell layer neurons compared to control animals which show a reduction in ganglion cell axons and a 44% loss of ganglion cell layer neurons; protection of retinal ganglion cell neurons persists at 18 weeks after injury

vision/eye

decreased retina ganglion cell number ( J:196076 )

• 6 weeks after optic nerve crush, tamoxifen-treated mice retain their ganglion cell axons and show only 13% loss of ganglion cell layer neurons compared to control animals which show a reduction in ganglion cell axons and a 44% loss of ganglion cell layer neurons; protection of retinal ganglion cell neurons persists at 18 weeks after injury

Genotype
MGI:5552951

cn132

• Allelic Composition: Pdpn^tm2.1Mlkn/Pdpn^tm2.1Mlkn; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

cardiovascular system

abnormal blood vessel morphology ( J:205423 )

• mucosal high endothelial venule (HEV) junctions in tamoxifen-treated mice resemble those of reactive peripheral HEVs

hemorrhage ( J:205423 )

• beginning at P15, tamoxifen-treated mice exhibit massive bleeding primarily in mucosal lymph nodes (mesenteric and cervical) but rarely in peripheral (inguinal and popliteal) lymph nodes with extravasation of red blood cells around high endothelial venules

• ovalbumin and CFA challenged tamoxifen-treated mice develop bleeding in draining peripheral lymph nodes of tamoxifen-treated mice

• treatment with Mel-14 reduces bleeding in draining peripheral lymph nodes of tamoxifen-treated mice

increased vascular permeability ( J:205423 )

• extravasation of red blood cells around high endothelial venules (HEVs) in lymph nodes from tamoxifen-treated mice

• FITC-dextran leaks from HEVs in tamoxifen-treated mice

• however, non-HEV blood vessels in lymph nodes and other organs do not leak FITC-dextran

immune system

abnormal lymph node morphology ( J:205423 )

• loss of mucosal and peripheral lymph nodes in tamoxifen-treated mice

absent peripheral lymph nodes ( J:205423 )

• loss of mucosal and peripheral lymph nodes in tamoxifen-treated mice

Genotype
MGI:5898009

cn133

• Allelic Composition: Ino80^tm1Schg/Ino80^tm1Schg; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:221224 )

• 50% of mice die by 170 days after 3 tamoxifen injections at 6-8 weeks of age

cellular

cellular phenotype ( J:221224 )

N • all phenotypes detected after cre induction in MEFs

abnormal telomere morphology ( J:221224 )

• a 1.7-fold increase in multiple telomeric signals (MTS, fragile telomeres); however, telomere length is not affected

abnormal cell physiology ( J:221224 )

• 4-hydroxytamoxifen (4-HT) treated MEFs are hypersensitive to hydroxyurea and aphidicolin, showing decreased colony forming after exposure

abnormal cell cycle ( J:221224 )

• defect in S-phase progression

increased cellular sensitivity to alkylating agents ( J:221224 )

• decreased survival of following exposure to hydroxyurea or aphicicolin

increased cellular sensitivity to hydroxyurea ( J:221224 )

increased cellular sensitivity to ultraviolet irradiation ( J:221224 )

• decreased survival 48h after UV exposure

decreased fibroblast proliferation ( J:221224 )

• cells stopped proliferation 4 days after cre induction

early cellular replicative senescence ( J:221224 )

• a higher percentage of 4-HT treated MEFs show increased staining at early passages for the senescence marker SA-beta-galactosidase which correlates with induction of p21 expression suggesting premature entry into cellular senescence/cell cycle arrest

abnormal DNA repair ( J:221224 )

• MEFs exposed to UV following 4-HT treatment exhibit a reduction in the efficiency of UV repair by the nucleotide excision repair pathway, showing delayed removal of UV-induced photo lesions and decreased cellular survival 48 hours after UV exposure

abnormal double-strand DNA break repair ( J:221224 )

• reduced efficiency of repair of ionizing radiation-induced double-stranded breaks, UV-induced photo lesions and dysfunctional telomeres

abnormal DNA replication ( J:221224 )

• 4-HT treated MEFs exhibit defects in ssDNA formation and telomere replication

• 4-HT treated MEFs exhibit a 1.7-fold increase in the number of multiple telomere signals, indicating defects in telomere replication

growth/size/body

decreased body weight ( J:221224 )

• mice injected with tamoxifen at 6-8 weeks of age exhibit reduced body weight

homeostasis/metabolism

abnormal DNA repair ( J:221224 )

• MEFs exposed to UV following 4-HT treatment exhibit a reduction in the efficiency of UV repair by the nucleotide excision repair pathway, showing delayed removal of UV-induced photo lesions and decreased cellular survival 48 hours after UV exposure

abnormal double-strand DNA break repair ( J:221224 )

• reduced efficiency of repair of ionizing radiation-induced double-stranded breaks, UV-induced photo lesions and dysfunctional telomeres

abnormal DNA replication ( J:221224 )

• 4-HT treated MEFs exhibit defects in ssDNA formation and telomere replication

• 4-HT treated MEFs exhibit a 1.7-fold increase in the number of multiple telomere signals, indicating defects in telomere replication

abnormal response to radiation ( J:221224 )

• reduced efficiency of repair of ionizing radiation-induced double-stranded breaks

neoplasm

neoplasm ( J:221224 )

N • tamoxifen treated mice do not exhibit increased tumor incidence

Genotype
MGI:6198665

cn134

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-MFN2*T105M)Dple}/Gt(ROSA)26Sor⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:251584 )

• mice develop a diseased phenotype beginning 4-6 weeks following tamoxifen treatment, with multiple organ failure leading to lethality

respiratory system

respiratory distress ( J:251584 )

• mice develop respiratory distress 4-6 weeks after tamoxifen treatment

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:251584 )

• mice exhibit loss of mobility 4-6 weeks after tamoxifen treatment

cellular

abnormal mitochondrial morphology ( J:251584 )

• tamoxifen-treated mice exhibit mitochondrial aggregation in renal cortex and liver parenchyma and small mitochondria aggregation in Schwann cell cytoplasm of the sciatic nerve, most likely indicating un-fused mitochondria

homeostasis/metabolism

ascites ( J:251584 )

• mice develop bloating due to ascites accumulation 4-6 weeks after tamoxifen treatment

integument

abnormal hair follicle morphology ( J:251584 )

• mice exhibit skin follicle erection 4-6 weeks after tamoxifen treatment

nervous system

abnormal myelination ( J:251584 )

• tamoxifen-treated mice show abnormal myelination of the tibial nerve, with abnormal myelin configurations surrounding some axons

• tibial nerves of tamoxifen-treated mice show double myelinated axons in which the inner portion of the outer sheath is decompacting

Genotype
MGI:6451097

cn135

• Allelic Composition: Nup85^tm1.1Yter/Nup85^tm1.1Yter; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

hematopoietic system

decreased macrophage cell number ( J:292726 )

• fewer macrophages in induced tumor tissue

• reduced CD206+ proportion of M2 macrophages in induced tumor tissue

decreased Ly6C high monocyte number ( J:292726 )

• fewer monocytes in induced tumor tissue

decreased Ly6C low monocyte number ( J:292726 )

• fewer monocytes in induced tumor tissue

immune system

decreased macrophage cell number ( J:292726 )

• fewer macrophages in induced tumor tissue

• reduced CD206+ proportion of M2 macrophages in induced tumor tissue

decreased Ly6C high monocyte number ( J:292726 )

• fewer monocytes in induced tumor tissue

decreased Ly6C low monocyte number ( J:292726 )

• fewer monocytes in induced tumor tissue

neoplasm

decreased tumor growth/size ( J:292726 )

• reduced size of induced tumors

Genotype
MGI:7316744

cn136

• Allelic Composition: Tcfl5^tm1Frem/Tcfl5^tm1Frem; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

reproductive system

azoospermia ( J:326601 )

♂ • adult tamoxifen-treated males lack spermatozoa in the seminiferous tubule lumen

abnormal spermatid morphology ( J:326601 )

♂ • adult tamoxifen-treated males show alterations in spermatid elongation resulting in aberrant spermatid morphology

multinucleated giant male germ cells ( J:326601 )

♂ • adult tamoxifen-treated males exhibit multinucleated round giant cells containing primary spermatocytes in most seminiferous tubules

abnormal seminiferous tubule morphology ( J:326601 )

♂ • adult tamoxifen-treated males show abnormal tubule morphology features, including multinucleated rounded giant cells containing primary spermatocytes, a decreased number of elongated spermatids, and no spermatozoa in the lumen

small testis ( J:326601 )

♂ • adult tamoxifen-treated males exhibit a significantly smaller testis size than control males

decreased testis weight ( J:326601 )

♂ • adult tamoxifen-treated males exhibit a significantly lower testis weight than control males

arrest of male meiosis ( J:326601 )

♂

abnormal spermiogenesis ( J:326601 )

♂ • adult tamoxifen-treated males show a 4.5-fold increase in the % of elongated spermatids with aberrant morphology relative to non-treated control males

male infertility ( J:326601 )

♂

cellular

azoospermia ( J:326601 )

♂ • adult tamoxifen-treated males lack spermatozoa in the seminiferous tubule lumen

abnormal spermatid morphology ( J:326601 )

♂ • adult tamoxifen-treated males show alterations in spermatid elongation resulting in aberrant spermatid morphology

multinucleated giant male germ cells ( J:326601 )

♂ • adult tamoxifen-treated males exhibit multinucleated round giant cells containing primary spermatocytes in most seminiferous tubules

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:326601 )

♂ • adult tamoxifen-treated males show abnormal tubule morphology features, including multinucleated rounded giant cells containing primary spermatocytes, a decreased number of elongated spermatids, and no spermatozoa in the lumen

small testis ( J:326601 )

♂ • adult tamoxifen-treated males exhibit a significantly smaller testis size than control males

decreased testis weight ( J:326601 )

♂ • adult tamoxifen-treated males exhibit a significantly lower testis weight than control males

Genotype
MGI:3821885

cn137

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0; Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0
• Genetic Background: involves: C57BL/6 * CBA * DBA/2

skeleton

skeleton phenotype ( J:142253 )

N • unlike mice treated with adenoviral cre, tamoxifen treated mice exhibit normal ossification and joint mobility

abnormal skeleton morphology ( J:142253 )

• tamoxifen treated mice injected with a control adenovirus exhibit decreased limb motion and small ectopic calcifications by P14

muscle

muscle phenotype ( J:142253 )

N • unlike mice treated with adenoviral cre, tamoxifen treated mice exhibit normal myocytes

Genotype
MGI:4360394

cn138

• Allelic Composition: Prom1^{tm1.1(DTA)Toko}/Prom1^{tm1.1(DTA)Toko}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA * SJL

nervous system

increased brain apoptosis ( J:152390 )

• tamoxifen treated mice exhibit increased apoptosis in the granular layer of the cerebellum, cortex of telencephalon, white matter and midbrain unlike similarly treated and untreated control mice

• however, ventricular zone cells and their neurogenesis are normal in tamoxifen treated mice

growth/size/body

decreased body weight ( J:152390 )

• tamoxifen treated mice exhibit reduced body weight compared with untreated and treated control mice

behavior/neurological

ataxia ( J:152390 )

• tamoxifen treated mice exhibit walking abnormalities

cellular

increased brain apoptosis ( J:152390 )

• tamoxifen treated mice exhibit increased apoptosis in the granular layer of the cerebellum, cortex of telencephalon, white matter and midbrain unlike similarly treated and untreated control mice

• however, ventricular zone cells and their neurogenesis are normal in tamoxifen treated mice

Genotype
MGI:5607628

cn139

• Allelic Composition: Abcg5^tm1.1Hobb/Abcg5^tm1.1Hobb; Abcg8^tm1.1Hobb/Abcg8^tm1.1Hobb; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: C57BL/6 * CBA * SJL

cellular

abnormal cellular cholesterol metabolism ( J:215443 )

• levels of sitosterol and campesterol are decreased in gallbladder as compared to controls

decreased cholesterol efflux ( J:215443 )

♂ • decreased amount of cholesterol is excreted into the feces as compared to controls

♂ • decreased amount of cholesterol is excreted into the bile as compared to controls

digestive/alimentary system

increased intestinal phytosterol absorption ( J:215443 )

♂ • fractional absorption of the phytosterols, sitosterol and campesterol, is increased

abnormal feces composition ( J:215443 )

♂

homeostasis/metabolism

abnormal cellular cholesterol metabolism ( J:215443 )

• levels of sitosterol and campesterol are decreased in gallbladder as compared to controls

decreased cholesterol efflux ( J:215443 )

♂ • decreased amount of cholesterol is excreted into the feces as compared to controls

♂ • decreased amount of cholesterol is excreted into the bile as compared to controls

increased intestinal phytosterol absorption ( J:215443 )

♂ • fractional absorption of the phytosterols, sitosterol and campesterol, is increased

decreased cholesterol level ( J:215443 )

♀ • decreased cholesterol levels in bile, liver and enterocytes as compared to controls

decreased circulating cholesterol level ( J:215443 )

♀ • decreased levels of circulating cholesterol as compared to controls

abnormal phytosterol level ( J:215443 )

decreased phytosterol level ( J:215443 )

♀ • levels of sitosterol and campesterol are decreased in gallbladder as compared to controls

increased phytosterol level ( J:215443 )

♀ • increased levels of sitosterol and campesterol in liver as compared to controls

♀ • increased levels of phytosterols in enterocytes

increased circulating phytosterol level ( J:215443 )

• mean plasma levels of sitosterol and campesterol are increased by 95-fold and 14-fold respectively, as compared to controls

• D4-sitostanol levels in plasma are increased as compared to controls

• D7-sitosterol levels in plasma are increased as compared to controls

Genotype
MGI:5810739

cn140

• Allelic Composition: Nkx2-5^tm1.1Gum/Nkx2-5^tm1.1Gum; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6J

muscle

abnormal pyloric sphincter morphology ( J:228275 )

• embryos treated with tamoxifen at E16.5 show a pyloric sphincter constriction that is 33% wider than that in wild-type controls at E18.5

• however, positioning of the epithelial pyloric border is normal at E18.5

abnormal stomach smooth muscle circular layer morphology ( J:228275 )

• embryos treated with tamoxifen at E14.5 show an altered shape of the dorsal inner circular muscle (ICM) at E16.5

abnormal stomach smooth muscle outer longitudinal layer morphology ( J:228275 )

• embryos treated with tamoxifen at E14.5 show a nearly complete absence of the alpha-smooth muscle actin (alpha-SMA)-positive dorsal pyloric outer longitudinal muscle (OLM) at E16.5, suggesting impaired maturation of the pyloric OLM fascicle

• embryos treated with tamoxifen at E16.5 (when OLM is already formed and strongly alpha-SMA-positive) show severe attenuation or regression of the dorsal pyloric OLM by E18.5

• remaining cells appear loosely organized and only weakly alpha-SMA positive

cellular

increased apoptosis ( J:228275 )

• embryos treated with tamoxifen at E14.5 show a ~2-fold increase in the proportion of caspase 3-positive cells within the pyloric OLM at E16.5 relative to wild-type controls

• however, no significant changes in apoptosis are detected within the ICM

decreased cell proliferation ( J:228275 )

• embryos treated with tamoxifen at E14.5 show a 25% decrease in the proportion of BrdU-positive cells in the pyloric OLM fascicle at E16.5 relative to wild-type controls

• however, no significant changes in proliferation are detected within the inner circular muscle (ICM)

digestive/alimentary system

abnormal pyloric sphincter morphology ( J:228275 )

• embryos treated with tamoxifen at E16.5 show a pyloric sphincter constriction that is 33% wider than that in wild-type controls at E18.5

• however, positioning of the epithelial pyloric border is normal at E18.5

abnormal stomach smooth muscle circular layer morphology ( J:228275 )

• embryos treated with tamoxifen at E14.5 show an altered shape of the dorsal inner circular muscle (ICM) at E16.5

abnormal stomach smooth muscle outer longitudinal layer morphology ( J:228275 )

• embryos treated with tamoxifen at E14.5 show a nearly complete absence of the alpha-smooth muscle actin (alpha-SMA)-positive dorsal pyloric outer longitudinal muscle (OLM) at E16.5, suggesting impaired maturation of the pyloric OLM fascicle

• embryos treated with tamoxifen at E16.5 (when OLM is already formed and strongly alpha-SMA-positive) show severe attenuation or regression of the dorsal pyloric OLM by E18.5

• remaining cells appear loosely organized and only weakly alpha-SMA positive

Genotype
MGI:5903287

cn141

• Allelic Composition: Dhps^{tm2c(EUCOMM)Wtsi}/Dhps^{tm2c(EUCOMM)Wtsi}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * CBA * SJL

mortality/aging

premature death ( J:236582 )

• 5 to 14 days after tamoxifen treatment

hematopoietic system

decreased bone marrow cell number ( J:236582 )

• of all three cell lines after tamoxifen treatment

decreased spleen red pulp amount ( J:236582 )

• after tamoxifen treatment

spleen hypoplasia ( J:236582 )

• after tamoxifen treatment

growth/size/body

decreased body weight ( J:236582 )

• in tamoxifen-treated mice

cachexia ( J:236582 )

• in tamoxifen-treated mice due to wasting syndrome

renal/urinary system

increased kidney iron level ( J:236582 )

• enhanced ferrous iron incorporation in the kidney of 2 of 4 tamoxifen-treated mice

homeostasis/metabolism

increased kidney iron level ( J:236582 )

• enhanced ferrous iron incorporation in the kidney of 2 of 4 tamoxifen-treated mice

immune system

decreased spleen red pulp amount ( J:236582 )

• after tamoxifen treatment

spleen hypoplasia ( J:236582 )

• after tamoxifen treatment

Genotype
MGI:6870515

cn142

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj

cellular

abnormal autophagosome formation ( J:258511 )

• after 12 h of nutrient deprivation, tamoxifen-treated mouse embryonic fibroblasts (MEFs) fail to show canonical autophagosome formation (punctate LC3 signal), unlike wild-type MEFs

homeostasis/metabolism

abnormal autophagosome formation ( J:258511 )

• after 12 h of nutrient deprivation, tamoxifen-treated mouse embryonic fibroblasts (MEFs) fail to show canonical autophagosome formation (punctate LC3 signal), unlike wild-type MEFs

Genotype
MGI:6192376

cn143

• Allelic Composition: Kdm6a^tm1Cdcn/Kdm6a^tm1Cdcn; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6J * CBA

mortality/aging

premature death ( J:263565 )

• some tamoxifen-treated mice die between 6 and 20 months of age

neoplasm

increased chronic myelocytic leukemia incidence ( J:263565 )

• tamoxifen treated mice have hypersegmented neutrophils, immature cells with myelomonocytic features, nucleated red blood cells, biolobed granulocytes, pseudo-Pelger-Huet cells, and megaplatelets, indicating the presence of myelodysplasia

• 9 of 12 mice exhibit myeloproliferative/myelodysplastic neoplasm within 6 months of tamoxifen treatment similar to human chronic myelomonocytic leukemia

hematopoietic system

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

extramedullary hematopoiesis ( J:263565 )

• in tamoxifen treated mice

increased granulocyte monocyte progenitor cell number ( J:263565 )

• increase in number of granulocyte-macrophage progenitor (GMP) cells in the bone marrow of tamoxifen treated mice

decreased erythroid progenitor cell number ( J:263565 )

• the number of burst forming unit-erythroid colonies decreases from 14 to 40 weeks of age in tamoxifen treated mice

decreased erythrocyte cell number ( J:263565 )

• decrease in number of red blood cells in tamoxifen treated mice

increased nucleated erythrocyte cell number ( J:263565 )

• in tamoxifen treated mice

increased granulocyte number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased neutrophil cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen

• however, B-cell and T-cell numbers are normal in tamoxifen treated mice

thrombocytopenia ( J:263565 )

• decrease in number of platelets in tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased myeloid cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+ myeloid cells in spleen

• increase in number of myeloid cells in peripheral blood of tamoxifen treated mice

increased hematopoietic stem cell number ( J:263565 )

• an increase in the number and proportion of hematopoietic stem cells (HSCs), including long-term HSCs and short-term HSCs in the bone marrow of tamoxifen treated mice

• however, the number of bone marrow cells is normal

decreased megakaryocyte-erythroid progenitor cell number ( J:263565 )

• decrease in number of megakaryocyte-erythroid progenitor (MEP) cells in the bone marrow of tamoxifen treated mice

abnormal hematopoietic stem cell physiology ( J:263565 )

• increase in serial replating capacity of the bone marrow, LSK (Lin-cKit+Sca1+) and GMP cells from tamoxifen treated mice, indicating an increase in the self-renewal potential of HSCs and progenitor cells

• in vitro assays suggest a differentiation bias of bone marrow and LSK cells toward the myeloid lineage, with an increase in the number of granulocyte-macrophage and granulocyte colonies and decrease in the number of burst forming unit-erythroid colonies

immune system

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

increased granulocyte number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased neutrophil cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen

• however, B-cell and T-cell numbers are normal in tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

growth/size/body

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myelomonocytic leukemia		DOID:0080188		J:263565

Genotype
MGI:6376225

cn144

• Allelic Composition: Emc3^em1Xjz/Emc3^em1Xjz; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6J * CBA

vision/eye

abnormal photoreceptor outer segment morphology ( J:280458 )

• reduced Rho trafficking to the outer segment in tamoxifen-treated mice

thin retina outer nuclear layer ( J:280458 )

• at P31, but not P27, in tamoxifen-treated mice

retina degeneration ( J:280458 )

• in the outer segment of tamoxifen-treated mice

nervous system

abnormal photoreceptor outer segment morphology ( J:280458 )

• reduced Rho trafficking to the outer segment in tamoxifen-treated mice

Genotype
MGI:6192375

cn145

• Allelic Composition: Kdm6a^tm1Cdcn/Y; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6J * CBA

mortality/aging

premature death ( J:263565 )

• some tamoxifen-treated mice die between 6 and 20 months of age

neoplasm

increased chronic myelocytic leukemia incidence ( J:263565 )

• tamoxifen treated mice have hypersegmented neutrophils, immature cells with myelomonocytic features, nucleated red blood cells, biolobed granulocytes, pseudo-Pelger-Huet cells, and megaplatelets, indicating the presence of myelodysplasia

• 7 of 11 mice exhibit myeloproliferative/myelodysplastic neoplasm within 10 months of tamoxifen treatment similar to human chronic myelomonocytic leukemia

hematopoietic system

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

extramedullary hematopoiesis ( J:263565 )

• in tamoxifen treated mice

increased granulocyte monocyte progenitor cell number ( J:263565 )

• increase in number of granulocyte-macrophage progenitor (GMP) cells in the bone marrow of tamoxifen treated mice

decreased erythroid progenitor cell number ( J:263565 )

• the number of burst forming unit-erythroid colonies decreases from 14 to 40 weeks of age in tamoxifen treated mice

decreased erythrocyte cell number ( J:263565 )

• decrease in number of red blood cells in tamoxifen treated mice

increased nucleated erythrocyte cell number ( J:263565 )

• in tamoxifen treated mice

increased granulocyte number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased neutrophil cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen

• however, B-cell and T-cell numbers are normal in tamoxifen treated mice

thrombocytopenia ( J:263565 )

• decrease in number of platelets in tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased myeloid cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+ myeloid cells in spleen

• increase in number of myeloid cells in peripheral blood of tamoxifen treated mice

increased hematopoietic stem cell number ( J:263565 )

• an increase in the number and proportion of hematopoietic stem cells (HSCs), including long-term HSCs and short-term HSCs in the bone marrow of tamoxifen treated mice

• however, the number of bone marrow cells is normal

decreased megakaryocyte-erythroid progenitor cell number ( J:263565 )

• decrease in number of megakaryocyte-erythroid progenitor (MEP) cells in the bone marrow of tamoxifen treated mice

abnormal hematopoietic stem cell physiology ( J:263565 )

• increase in serial replating capacity of the bone marrow, LSK (Lin-cKit+Sca1+) and GMP cells from tamoxifen treated mice, indicating an increase in the self-renewal potential of HSCs and progenitor cells

• in vitro assays suggest a differentiation bias of bone marrow and LSK cells toward the myeloid lineage, with an increase in the number of granulocyte-macrophage and granulocyte colonies and decrease in the number of burst forming unit-erythroid colonies

immune system

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

increased granulocyte number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased neutrophil cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen

• however, B-cell and T-cell numbers are normal in tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

growth/size/body

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myelomonocytic leukemia		DOID:0080188		J:263565

Genotype
MGI:6159281

cn146

• Allelic Composition: Fam210a^{tm1c(EUCOMM)Wtsi}/Fam210a^{tm1c(EUCOMM)Wtsi}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6N * CBA * SJL

mortality/aging

premature death ( J:261817 )

• tamoxifen-treated mice die between 63 and 70 days after birth

skeleton

increased osteoclast cell number ( J:261817 )

• in tamoxifen-treated mice

decreased bone mineral content ( J:261817 )

• in tamoxifen-treated mice

decreased bone mineral density ( J:261817 )

• in tamoxifen-treated mice

decreased compact bone volume ( J:261817 )

• in tamoxifen-treated mice

decreased trabecular bone volume ( J:261817 )

• in tamoxifen-treated mice

decreased compact bone thickness ( J:261817 )

• in tamoxifen-treated mice

decreased bone trabecula number ( J:261817 )

• in tamoxifen-treated mice

increased bone trabecular spacing ( J:261817 )

• with increased structural model index in tamoxifen-treated mice

decreased bone ossification ( J:261817 )

• in cortical and trabecular bones of tamoxifen-treated mice

decreased bone strength ( J:261817 )

• in tamoxifen-treated mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:261817 )

N • tamoxifen-treated mice exhibit normal serum levels of calcium, phosphate, urea nitrogen and total protein

behavior/neurological

decreased grip strength ( J:261817 )

• in tamoxifen-treated mice

limbs/digits/tail

abnormal limb morphology ( J:261817 )

• decreased lean muscle mass in all limbs of tamoxifen-treated mice

growth/size/body

decreased body weight ( J:261817 )

• from 49 days after birth in tamoxifen-treated mice

immune system

increased osteoclast cell number ( J:261817 )

• in tamoxifen-treated mice

hematopoietic system

increased osteoclast cell number ( J:261817 )

• in tamoxifen-treated mice

Genotype
MGI:5607147

cn147

• Allelic Composition: Pou4f1^tm1.1Gan/Pou4f1^tm1.1Gan; Pou4f2^tm2.1Gan/Pou4f2^tm2.1Gan; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: Not Specified

vision/eye

vision/eye phenotype ( J:215207 )

N • mice treated with tamoxifen exhibit normal retinal interneurons, Muller glial cells, and optic nerves and normal survival of adult retinal ganglion cells under normal conditions

abnormal eye physiology ( J:215207 )

• death of retinal ganglion cells in tamoxifen treated mice at 3 days post controlled optic nerve crush is initially delayed but this difference is no longer present at 5 days after crush, indicating impaired acute response to damage

Genotype
MGI:5469878

cx148

• Allelic Composition: Syngap1^tm2Geno/Syngap1⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

behavior/neurological

abnormal behavior ( J:193208 )

• mice exhibit behavioral abnormalities as in Syngap1^tm1Rlh heterozygotes

abnormal spatial working memory ( J:193208 )

• untreated mice and mice treated with tamoxifen in adulthood exhibit absence of spontaneous alteration in a T-maze compared with control mice

decreased anxiety-related response ( J:193208 )

• untreated mice and mice treated with tamoxifen in adulthood spend increased time in open arms of an elevated plus maze compared with control mice

hyperactivity ( J:193208 )

• untreated mice and mice treated with tamoxifen in adulthood exhibit increased activity in an open field compared with control mice

Genotype
MGI:3850051

cx149

• Allelic Composition: Nlrp3^tm2Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

growth/size/body

slow postnatal weight gain ( J:150054 )

• some older mice have slower weight gain

immune system

skin inflammation ( J:150054 )

• some older mice develop skin inflammation suggesting leaky expression of the cre recombinase

integument

skin inflammation ( J:150054 )

• some older mice develop skin inflammation suggesting leaky expression of the cre recombinase

Genotype
MGI:3850049

cx150

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

growth/size/body

slow postnatal weight gain ( J:150054 )

• some older mice have slower weight gain

immune system

skin inflammation ( J:150054 )

• some older mice develop skin inflammation suggesting leaky expression of the cre recombinase

integument

skin inflammation ( J:150054 )

• some older mice develop skin inflammation suggesting leaky expression of the cre recombinase

Genotype
MGI:3845073

tg151

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

digestive/alimentary system

abnormal stomach glandular region morphology ( J:163367 )

• occasional regenerative foci consisting of tortuous glandular structures of highly proliferative cells in tamoxifen-treated mice

• glandular cysts in tamoxifen-treated mice

abnormal gastric parietal cell morphology ( J:163367 )

• atrophied with expanded mesenchyme around gastric units in tamoxifen-treated mice

• however, some mice recover from cre genotoxicity-induced injury

abnormal stomach epithelium morphology ( J:163367 )

• profound remodeling of the corpus gastric epithelium with nearly complete replacement by stromal cells at 14 days in tamoxifen-treated mice

abnormal digestive system physiology ( J:163367 )

• increased gastric parietal cell proliferation in tamoxifen-treated mice

• increased apoptosis in the stomach of tamoxifen-treated mice

cellular

increased apoptosis ( J:163367 )

• with increased DNA damage in the stomach of tamoxifen-treated mice

• however, titration of tamoxifen dosage and frequency reduces cre genotoxicity

endocrine/exocrine glands

abnormal gastric parietal cell morphology ( J:163367 )

• atrophied with expanded mesenchyme around gastric units in tamoxifen-treated mice

• however, some mice recover from cre genotoxicity-induced injury

Genotype
MGI:3716206

tg152

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: C57BL/6 * CBA

neoplasm

neoplasm ( J:114992 )

N • no tumors are observed up to 12 months of age