Phenotypes associated with this allele

• Allele Symbol: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}
• Allele Name: transgene insertion 1, Eric J Brown
• Allele ID: MGI:3707333
• Summary: 57 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Igf1r^tm1Jcbr/Igf1r^tm1Jcbr Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	B6.Cg-Ndor1^Tg(UBC-cre/ERT2)1Ejb Igf1r^tm1Jcbr	MGI:5904250
cn2	Zfp574^em3Btlr/Zfp574^em3Btlr Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	B6.Cg-Ndor1^Tg(UBC-cre/ERT2)1Ejb Zfp574^em3Btlr	MGI:7790547
cn3	Zfp574^em3Btlr/Zfp574^em3Btlr Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Tg(IghMyc)22Bri/0	B6.Cg-Ndor1^Tg(UBC-cre/ERT2)1Ejb Zfp574^em3Btlr Tg(IghMyc)22Bri	MGI:7790549
cn4	Stk26^tm1.1Zzh/Stk26^tm1.1Zzh Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129 * 129P2/OlaHsd * C57BL/6 * SJL	MGI:6695866
cn5	Stk26^tm1.1Zzh/Stk26^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129 * 129P2/OlaHsd * C57BL/6 * SJL	MGI:6695867
cn6	Adcy3^tm2.1Drs/Adcy3^tm2.1Drs Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129 * 129X1/SvJ * C57BL/6	MGI:7260162
cn7	Fus^tm1a(EUCOMM)Wtsi/Fus^tm1c(EUCOMM)Wtsi Mapt^tm3.1(FUS)Neas/Mapt^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129 * C3H * C57BL/6 * C57BL/6N	MGI:5824116
cn8	Eif4b^tm1.1Smoc/Eif4b^tm1.1Smoc Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129 * C57BL/6	MGI:6790428
cn9	Lepr^tm1Rck/Lepr^tm1Rck Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129 * C57BL/6	MGI:7782473
cn10	Ccbe1^tm2.1Mlkn/Ccbe1^tm2.1Mlkn Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129 * C57BL/6	MGI:5495740
cn11	Kmt2b^tm1.1Afst/Kmt2b^tm1.1Afst Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129P2/OlaHsd * 129S/Sv * C3H/HeH * C57BL/6	MGI:5532302
cn12	Hif1a^tm3Rsjo/Hif1a^tm3Rsjo Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3710347
cn13	Esco2^tm1.1Ge/Esco2^tm1.1Ge Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:6828779
cn14	Esco1^tm1.1Ge/Esco1^tm1.1Ge Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:6828777
cn15	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Stag2^tm1.1Alos/Y	involves: 129S6/SvEvTac * C57BL/6NCrl	MGI:6490363
cn16	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Stag2^tm1.1Alos/Stag2^tm1.1Alos	involves: 129S6/SvEvTac * C57BL/6NCrl	MGI:6490362
cn17	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Rpl11^tm1.1Srn/Rpl11^+	involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1	MGI:6510523
cn18	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Rpl11^tm1.1Srn/Rpl11^tm1.1Srn	involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1	MGI:6510297
cn19	Rad51^tm1Csha/Rad51^tm1Csha Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S/Sv * C57BL/6J	MGI:7311703
cn20	Fto^tm1.1Rdc/Fto^tm1.1Rdc Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5494567
cn21	Wnt5a^tm1.1Tpy/Wnt5a^tm1.1Tpy Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S1/Sv * C57BL/6	MGI:5440735
cn22	Atr^tm1Bal/Atr^tm2Bal Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S2/SvPas * C57BL/6	MGI:3717476
cn23	Col1a1^tm3(CAG-IDH2*R140Q)Kkw/Col1a1^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S4/SvJae * BALB/c * C57BL/6	MGI:5582193
cn24	Col1a1^tm2(CAG-IDH2*R172K)Kkw/Col1a1^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S4/SvJae * BALB/c * C57BL/6	MGI:5582235
cn25	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Rraga^tm2Dmsa/Rraga^tm2Dmsa	involves: 129S/SvEv * 129S4/SvJae * C57BL/6	MGI:6236293
cn26	Lin28b^tm1Gqda/Lin28b^tm1.1Gqda Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S4/SvJae * C57BL/6	MGI:5519073
cn27	Lin28a^tm1Gqda/Lin28a^tm1.1Gqda Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * FVB/N	MGI:5519072
cn28	Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^+ Ndufs4^tm1Rpa/Ndufs4^tm1Rpa Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6	MGI:4818647
cn29	Foxo1^tm1Flv/Foxo1^tm1Flv Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6	MGI:5448154
cn30	Bmp1^tm1.1Dgr/Bmp1^tm1.1Dgr Tll1^tm2.1Dgr/Tll1^tm2.1Dgr Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6 * SJL	MGI:5693162
cn31	Sh2d1a^tm1.1Knic/Y Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129X1/SvJ * C57BL/6	MGI:5502766
cn32	Sh2d1a^tm1.1Knic/Sh2d1a^tm1.1Knic Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129X1/SvJ * C57BL/6	MGI:5502763
cn33	Gt(ROSA)26Sor^tm1(Smo/EYFP)Amc/Gt(ROSA)26Sor^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129X1/SvJ * C57BL/6	MGI:6197802
cn34	Fus^tm1a(EUCOMM)Wtsi/Fus^tm1c(EUCOMM)Wtsi Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C3H * C57BL/6 * C57BL/6N	MGI:5824114
cn35	Igf1r^tm1Jcbr/Igf1r^tm1Jcbr Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6	MGI:5779542
cn36	Gt(ROSA)26Sor^tm1.1(DUX4*)Plj/Gt(ROSA)26Sor^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6	MGI:6120563
cn37	Lcn6^tm1.1Ylzh/Lcn6^tm1.1Ylzh Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S/SvEv * C57BL/6	MGI:6121436
cn38	Gm30731^tm1.1Dalm/Gm30731^tm1.1Dalm Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S/SvEv * C57BL/6	MGI:6385157
cn39	Dcp2^tm1Smoc/Dcp2^tm1Smoc Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S/SvEv * C57BL/6	MGI:6459915
cn40	Gt(ROSA)26Sor^tm2Iaai/Gt(ROSA)26Sor^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6	MGI:5496426
cn41	Gt(ROSA)26Sor^tm1Iaai/Gt(ROSA)26Sor^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6	MGI:5496425
cn42	Cxcl12^tm1.1Sjm/Cxcl12^tm1.1Sjm Ndor1^Tg(UBC-cre/ERT2)1Ejb/?	involves: 129S/SvEv * C57BL/6	MGI:5488603
cn43	Il2^tm1.1Kasm/Il2^tm1.1Kasm Ndor1^Tg(UBC-cre/ERT2)1Ejb/?	involves: 129S/SvEv * C57BL/6	MGI:5449733
cn44	Dido1^tm3Cmar/Dido1^tm3.1Cmar Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S/SvEv * C57BL/6	MGI:7343747
cn45	Armcx3^tm1.1Eso/Y Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+	involves: 129S/SvEv * C57BL/6	MGI:7612206
cn46	Phf2^tm1.2Yima/Phf2^tm1.2Yima Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6 * C57BL/6J * SJL	MGI:5496671
cn47	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Rnpc3^tm1c(EUCOMM)Wtsi/Rnpc3^tm1c(EUCOMM)Wtsi	involves: 129S/SvEv * C57BL/6 * C57BL/6N	MGI:6276277
cn48	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Rnpc3^tm1c(EUCOMM)Wtsi/Rnpc3^+	involves: 129S/SvEv * C57BL/6 * C57BL/6N	MGI:6276274
cn49	Pdzrn3^tm1.1Ysa/Pdzrn3^tm1.1Ysa Ndor1^Tg(UBC-cre/ERT2)1Ejb/?	involves: 129S/SvEv * C57BL/6 * C57BL/6NCrlj * CBA/JNCrlj	MGI:5749852
cn50	Nr6a1^tm1c(EUCOMM)Wtsi/Nr6a1^tm1c(EUCOMM)Wtsi Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6 * C57BL/6N * SJL	MGI:5532734
cn51	Kitl^tm2.1Sjm/Kitl^tm2.1Sjm Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6 * C57BL/Ka * SJL	MGI:5306350
cn52	Stk11^tm1.1Sjm/Stk11^tm1.1Sjm Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:4840218
cn53	Clec16a^tm1.1Hhak/Clec16a^tm1.1Hhak Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:5766642
cn54	Nsmce2^tm2.1Ofc/Nsmce2^tm2.1Ofc Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:5906758
cn55	Cdk7^Gt(D032B11)1.1Wrst/Cdk7^Gt(D032B11)1.1Wrst Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvPas * 129S2/SvPas * C57BL/6 * SJL	MGI:5429245
cn56	Epas1^tm1Mcs/Epas1^tm1.1Mcs Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129X1/SvJ * FVB/N	MGI:3710346
cx57	Ndor1^Tg(UBC-cre/ERT2)1Ejb/Ndor1^+ Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:6403623

Genotype
MGI:5904250

cn1

• Allelic Composition: Igf1r^tm1Jcbr/Igf1r^tm1Jcbr; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: B6.Cg-Ndor1^{Tg(UBC-cre/ERT2)1Ejb} Igf1r^tm1Jcbr

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

immune system

decreased susceptibility to type I hypersensitivity reaction ( J:241924 )

♀ • mice challenged with house dust mite extract show improved lung function, attenuated airway hyperresponsiveness and mucus secretion, decrease in blood and bronchioalveolar lavage fluid eosinophils, a decrease in lung IL13 levels and collagen levels, decrease in smooth muscle thickness and depletion of goblet cell metaplasia compared to controls

mortality/aging

abnormal susceptibility to injury induced morbidity/mortality ( J:241920 )

• tamoxifen treated mice treated with bleomycin to induce lung damage at 6 weeks of age show increased survival (79%) compared to controls (33%)

homeostasis/metabolism

decreased collagen level ( J:241924 )

♀ • house dust mite-induced increase in airway collagen content is reduced in tamoxifen treated mice

abnormal susceptibility to injury induced morbidity/mortality ( J:241920 )

• tamoxifen treated mice treated with bleomycin to induce lung damage at 6 weeks of age show increased survival (79%) compared to controls (33%)

decreased susceptibility to injury ( J:241920 )

• tamoxifen treated mice show protection against lung vascular fragility and permeability, reduced inflammatory cell presence in bronchioalveolar lavage fluid, reduced proliferation in lung perivascular areas and the alveolar parenchyma, reduced alveolar damage, and attenuation of acute lung inflammation and bone marrow neutrophilopoiesis after bleomycin-induced lung damage

respiratory system

decreased respiratory mucosa goblet cell number ( J:241924 )

♀ • house dust mite-induced goblet cell hyperplasia is reduced in tamoxifen treated mice

decreased airway responsiveness ( J:241924 )

♀ • house dust mite-induced airway hyperresponsiveness is attenuated in tamoxifen treated mice

Genotype
MGI:7790547

cn2

• Allelic Composition: Zfp574^em3Btlr/Zfp574^em3Btlr; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: B6.Cg-Ndor1^{Tg(UBC-cre/ERT2)1Ejb} Zfp574^em3Btlr

hematopoietic system

macrocytic anemia ( J:354285 )

• tamoxifen-treated mice exhibit macrocytic anemia

decreased B cell number ( J:354285 )

• transplantation of a 1:1 mixture of mutant and congenic wild-type bone marrow cells into lethally irradiated CD45.1 recipients that were injected with tamoxifen 12 weeks after bone marrow transplantation exhibit 40.3% elimination of mutant nonmalignant B cells

pancytopenia ( J:354285 )

• tamoxifen-treated mice exhibit pancytopenia with macrocytic anemia

abnormal hematopoietic stem cell morphology ( J:354285 )

• transplantation of a 1:1 mixture of mutant and congenic wild-type bone marrow cells into lethally irradiated CD45.1 recipients that were injected with tamoxifen at 12 weeks posttransplant show rapid deletion of all hematopoietic stem and progenitor cell (HSPC) populations derived specifically from mutant bone marrow; progenitor cell populations are more severely affected that hematopoietic stem cells

immune system

decreased B cell number ( J:354285 )

• transplantation of a 1:1 mixture of mutant and congenic wild-type bone marrow cells into lethally irradiated CD45.1 recipients that were injected with tamoxifen 12 weeks after bone marrow transplantation exhibit 40.3% elimination of mutant nonmalignant B cells

Genotype
MGI:7790549

cn3

• Allelic Composition: Zfp574^em3Btlr/Zfp574^em3Btlr; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Tg(IghMyc)22Bri/0
• Genetic Background: B6.Cg-Ndor1^{Tg(UBC-cre/ERT2)1Ejb} Zfp574^em3Btlr Tg(IghMyc)22Bri

hematopoietic system

decreased B cell number ( J:354285 )

• transplantation of a 1:1 mixture of mutant and wild-type bone marrow cells into lethally irradiated CD45.1 recipients that were injected with tamoxifen 12 weeks after bone marrow transplantation exhibit more rapid elimination of leukemic B cells than nonmalignant Zfp574^em3Btlr/Zfp574^em3Btlr Ndor1^{Tg(UBC-cre/ERT2)1Ejb} mice; up to 79.3% of established leukemic B cells are eliminated after the first dose of tamoxifen and 91.9% of leukemic B cells are eliminated after a second tamoxifen dose

immune system

decreased B cell number ( J:354285 )

• transplantation of a 1:1 mixture of mutant and wild-type bone marrow cells into lethally irradiated CD45.1 recipients that were injected with tamoxifen 12 weeks after bone marrow transplantation exhibit more rapid elimination of leukemic B cells than nonmalignant Zfp574^em3Btlr/Zfp574^em3Btlr Ndor1^{Tg(UBC-cre/ERT2)1Ejb} mice; up to 79.3% of established leukemic B cells are eliminated after the first dose of tamoxifen and 91.9% of leukemic B cells are eliminated after a second tamoxifen dose

neoplasm

decreased leukemia incidence ( J:354285 )

• transplantation of a 1:1 mixture of mutant and wild-type bone marrow cells into lethally irradiated CD45.1 recipients that were injected with tamoxifen 12 weeks after bone marrow transplantation exhibit more rapid elimination of leukemic B cells than nonmalignant Zfp574^em3Btlr/Zfp574^em3Btlr Ndor1^{Tg(UBC-cre/ERT2)1Ejb} mice; up to 79.3% of established leukemic B cells are eliminated after the first dose of tamoxifen and 91.9% of leukemic B cells are eliminated after a second tamoxifen dose

Genotype
MGI:6695866

cn4

• Allelic Composition: Stk26^tm1.1Zzh/Stk26^tm1.1Zzh; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6 * SJL

neoplasm

increased incidence of tumors by chemical induction ( J:289548 )

♀ • tamoxifen-induced 8-week-old mice treated with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) show an increase in the numbers of palpable gastric tumors compared to wild-type mice

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:289548 )

♀ • tamoxifen-induced 8-week-old mice treated with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) show an increase in the numbers of palpable gastric tumors compared to wild-type mice

Genotype
MGI:6695867

cn5

• Allelic Composition: Stk26^tm1.1Zzh/Stk26⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6 * SJL

neoplasm

increased incidence of tumors by chemical induction ( J:289548 )

♀ • tamoxifen-induced 8-week-old mice treated with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) show an increase in the numbers of palpable gastric tumors compared to wild-type mice

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:289548 )

♀ • tamoxifen-induced 8-week-old mice treated with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) show an increase in the numbers of palpable gastric tumors compared to wild-type mice

Genotype
MGI:7260162

cn6

• Allelic Composition: Adcy3^tm2.1Drs/Adcy3^tm2.1Drs; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129 * 129X1/SvJ * C57BL/6

behavior/neurological

abnormal response to new environment ( J:281839 )

• tamoxifen-administered adults show a slightly longer latency to feed than controls in the novelty-suppressed feeding test

behavioral despair ( J:281839 )

• adult mice administered tamoxifen orally show longer periods of immobility in the tail suspension test and the force swim test

decreased grooming behavior ( J:281839 )

• tamoxifen-administered adults exhibit a poor coat state, suggesting decreased grooming

hypoactivity ( J:281839 )

• tamoxifen-administered adults are less active than controls in their home cage during the night

abnormal circadian sleep/wake cycle ( J:281839 )

• tamoxifen-administered adults show altered sleep; the sleep-wake cycle is not very rhythmic

abnormal non-rapid eye movement sleep pattern ( J:281839 )

• mice have more NREM sleep in nighttime and less NREM sleep in daytime than controls

abnormal nest building behavior ( J:281839 )

• tamoxifen-administered adults perform poorly in nest building

homeostasis/metabolism

increased circulating corticosterone level ( J:281839 )

• tamoxifen-administered adults exhibit a higher level of corticosterone

Genotype
MGI:5824116

cn7

• Allelic Composition: Fus^{tm1a(EUCOMM)Wtsi}/Fus^{tm1c(EUCOMM)Wtsi}; Mapt^{tm3.1(FUS)Neas}/Mapt⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129 * C3H * C57BL/6 * C57BL/6N
• Cell Lines: EPD0667_5_C04

nervous system

abnormal neuromuscular synapse morphology ( J:232167 )

• mice treated with tamoxifen postnatally show denervation in the tibialis anterior muscle where about 12% of neuromuscular junctions are denervated

Genotype
MGI:6790428

cn8

• Allelic Composition: Eif4b^tm1.1Smoc/Eif4b^tm1.1Smoc; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

increased susceptibility to Orthomyxoviridae infection induced morbidity/mortality ( J:311140 )

• tamoxifen-treated mice infected with influenza virus lose more weight and die within 8 days compared to controls in which 30% survive at the end of the experiments

premature death ( J:311140 )

• majority of mice treated with tamoxifen at 10-12 weeks of age for 5 days die within 10 days

growth/size/body

weight loss ( J:311140 )

• mice show more body weight loss than controls after the first injection of tamoxifen

behavior/neurological

decreased food intake ( J:311140 )

• tamoxifen-treated mice exhibit loss of appetite

decreased locomotor activity ( J:311140 )

• tamoxifen-treated mice exhibit loss of motility

digestive/alimentary system

increased susceptibility to induced colitis ( J:311140 )

• tamoxifen-treated mice exhibit more severe dextran sulfate sodium (DSS)-induced colonic injury, with more weight loss, shorter colon length and more severe inflammation

endocrine/exocrine glands

small thymus ( J:311140 )

• thymus is smaller in tamoxifen-treated mice

hematopoietic system

small thymus ( J:311140 )

• thymus is smaller in tamoxifen-treated mice

increased neutrophil cell number ( J:311140 )

• tamoxifen-treated mice infected with influenza virus exhibit increased number of neutrophils or alveolar macrophages in the lungs

increased macrophage cell number ( J:311140 )

• tamoxifen-treated mice infected with influenza virus exhibit increased number of alveolar macrophages in the lungs

decreased leukocyte cell number ( J:311140 )

• tamoxifen treated mice show a decrease in the number of white blood cells

• however, no effect on numbers of red blood cells or platelets is seen

decreased lymphocyte cell number ( J:311140 )

• total number and the percentage of lymphocytes is decreased in peripheral blood cells of tamoxifen-treated mice

• tamoxifen-treated mice show a decrease in lymphocytes in the spleen and thymus

• percentage of CD4+ and CD8+ lymphocytes is reduced in lungs of tamoxifen-treated influenza A virus infected mice

decreased NK cell number ( J:311140 )

• tamoxifen-treated mice infected with influenza A virus show decreased natural killer cells in the lungs compared to controls

• tamoxifen-treated mice infected with influenza A show decreased number of IFN-gamma+ and CD107a+ natural killer cells indicating impaired infiltration of natural killer cells and their function in the lung in response to influenza A infection

small spleen ( J:311140 )

• spleen is smaller in tamoxifen-treated mice

immune system

increased susceptibility to induced colitis ( J:311140 )

• tamoxifen-treated mice exhibit more severe dextran sulfate sodium (DSS)-induced colonic injury, with more weight loss, shorter colon length and more severe inflammation

small thymus ( J:311140 )

• thymus is smaller in tamoxifen-treated mice

increased neutrophil cell number ( J:311140 )

• tamoxifen-treated mice infected with influenza virus exhibit increased number of neutrophils or alveolar macrophages in the lungs

increased macrophage cell number ( J:311140 )

• tamoxifen-treated mice infected with influenza virus exhibit increased number of alveolar macrophages in the lungs

decreased leukocyte cell number ( J:311140 )

• tamoxifen treated mice show a decrease in the number of white blood cells

• however, no effect on numbers of red blood cells or platelets is seen

decreased lymphocyte cell number ( J:311140 )

• total number and the percentage of lymphocytes is decreased in peripheral blood cells of tamoxifen-treated mice

• tamoxifen-treated mice show a decrease in lymphocytes in the spleen and thymus

• percentage of CD4+ and CD8+ lymphocytes is reduced in lungs of tamoxifen-treated influenza A virus infected mice

decreased NK cell number ( J:311140 )

• tamoxifen-treated mice infected with influenza A virus show decreased natural killer cells in the lungs compared to controls

• tamoxifen-treated mice infected with influenza A show decreased number of IFN-gamma+ and CD107a+ natural killer cells indicating impaired infiltration of natural killer cells and their function in the lung in response to influenza A infection

small spleen ( J:311140 )

• spleen is smaller in tamoxifen-treated mice

lung inflammation ( J:311140 )

• tamoxifen-treated mice infected with pseudorabies virus show increased percentages of neutrophils, alveolar macrophages and monocytes in the lungs, indicating enhanced pulmonary inflammation in response to viral infection

increased susceptibility to Orthomyxoviridae infection ( J:311140 )

• tamoxifen-treated mice show increased susceptibility to influenza A virus, showing a higher degree of acute lung injury, more severe inflammation and inflammatory cell infiltration in the lungs, higher protein levels of viral NP in the lungs and increased viral titers in the lungs compared to controls

increased susceptibility to Orthomyxoviridae infection induced morbidity/mortality ( J:311140 )

• tamoxifen-treated mice infected with influenza virus lose more weight and die within 8 days compared to controls in which 30% survive at the end of the experiments

integument

matted coat ( J:311140 )

• tamoxifen-treated mice exhibit matted hairs

respiratory system

lung inflammation ( J:311140 )

• tamoxifen-treated mice infected with pseudorabies virus show increased percentages of neutrophils, alveolar macrophages and monocytes in the lungs, indicating enhanced pulmonary inflammation in response to viral infection

Genotype
MGI:7782473

cn9

• Allelic Composition: Lepr^tm1Rck/Lepr^tm1Rck; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129 * C57BL/6

growth/size/body

obese ( J:344866 )

• mice gain approximately 17-19 grams over 4 weeks after tamoxifen treatment

homeostasis/metabolism

increased circulating leptin level ( J:344866 )

• tamoxifen-treated mice develop hyperleptinemia

• hyperleptinemia in tamoxifen-treated mice is resistant to auranofin treatment

decreased physiological sensitivity to xenobiotic ( J:344866 )

• tamoxifen-treated mice lack metabolic responses to the drug auranofin, with no effect on hyperleptinemia, food intake, respiratory exchange ratio, activity, insulin and glucose tolerance, fasting insulin levels, or fatty liver and auranofin treatment does not increase fasting serum free fatty acids as in wild-type mice

• tamoxifen-treated mice lack the anti-inflammatory responses to auranofin in epididymal white adipose tissue (eWAT) that are seen in wild-type mice and auranofin treatment does not increase eWAT oxygen consumption rates

Genotype
MGI:5495740

cn10

• Allelic Composition: Ccbe1^tm2.1Mlkn/Ccbe1^tm2.1Mlkn; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129 * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:196696 )

N • following postnatal tamoxifen hematocrits and erythropoiesis following phlebotomy are similar to controls

Genotype
MGI:5532302

cn11

• Allelic Composition: Kmt2b^tm1.1Afst/Kmt2b^tm1.1Afst; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv * C3H/HeH * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:203736 )

N • tamoxifen-treated mice exhibit normal glucose homeostasis

Genotype
MGI:3710347

cn12

• Allelic Composition: Hif1a^tm3Rsjo/Hif1a^tm3Rsjo; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

immune system

immune system phenotype ( J:119731 )

N • hematocrit levels are normal in mutants; mutants do not develop anemia

Genotype
MGI:6828779

cn13

• Allelic Composition: Esco2^tm1.1Ge/Esco2^tm1.1Ge; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

cellular

abnormal mitosis ( J:296958 )

• tamoxifen-treated mouse embryonic fibroblasts arrest in S-phase

Genotype
MGI:6828777

cn14

• Allelic Composition: Esco1^tm1.1Ge/Esco1^tm1.1Ge; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

cellular

abnormal mitosis ( J:296958 )

• tamoxifen-treated mouse embryonic fibroblasts arrest in G1

Genotype
MGI:6490363

cn15

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Stag2^tm1.1Alos/Y
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl

mortality/aging

premature death ( J:298088 )

♂ • 4 weeks after initiation of tamoxifen treatment

cellular

abnormal mitosis ( J:298088 )

♂ • tamoxifen-treated mouse embryonic fibroblasts exhibit increased chromosome adhesion and mis-segregation compared with control cells

increased fibroblast apoptosis ( J:298088 )

♂ • increased caspase-3-positive cells in tamoxifen-treated mouse embryonic fibroblasts

cellular necrosis ( J:298088 )

♂ • 8 week old tamoxifen-treated mice exhibit increased intestinal erosion and necrosis compared with wild-type mice

abnormal enterocyte proliferation ( J:298088 )

♂ • reduced in intestinal crypts of tamoxifen-treated mice indicating reduced cellular renewal

decreased fibroblast proliferation ( J:298088 )

♂ • increased doubling time in tamoxifen-treated mouse embryonic fibroblasts

digestive/alimentary system

abnormal enterocyte proliferation ( J:298088 )

♂ • reduced in intestinal crypts of tamoxifen-treated mice indicating reduced cellular renewal

abnormal intestine morphology ( J:298088 )

♂ • 8 week old tamoxifen-treated mice exhibit increased intestinal erosion and necrosis compared with wild-type mice

growth/size/body

decreased body weight ( J:298088 )

♂ • in tamoxifen-treated mice

hematopoietic system

hematopoietic system phenotype ( J:298088 )

♂N • tamoxifen-treated mice exhibit normal adult hematopoiesis

abnormal hematopoietic stem cell physiology ( J:298088 )

♂ • enhanced self-renewal in cells from tamoxifen-treated mice

neoplasm

neoplasm ( J:298088 )

♂N • tamoxifen-treated mice do not exhibit increased spontaneous tumors

Genotype
MGI:6490362

cn16

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Stag2^tm1.1Alos/Stag2^tm1.1Alos
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl

mortality/aging

premature death ( J:298088 )

♀ • 4 weeks after initiation of tamoxifen treatment

cellular

abnormal mitosis ( J:298088 )

♀ • tamoxifen-treated mouse embryonic fibroblasts exhibit increased chromosome adhesion and mis-segregation compared with control cells

increased fibroblast apoptosis ( J:298088 )

♀ • increased caspase-3-positive cells in tamoxifen-treated mouse embryonic fibroblasts

cellular necrosis ( J:298088 )

♀ • 8 week old tamoxifen-treated mice exhibit increased intestinal erosion and necrosis compared with wild-type mice

abnormal enterocyte proliferation ( J:298088 )

♀ • reduced in intestinal crypts of tamoxifen-treated mice indicating reduced cellular renewal

decreased fibroblast proliferation ( J:298088 )

♀ • increased doubling time in tamoxifen-treated mouse embryonic fibroblasts

digestive/alimentary system

abnormal enterocyte proliferation ( J:298088 )

♀ • reduced in intestinal crypts of tamoxifen-treated mice indicating reduced cellular renewal

abnormal intestine morphology ( J:298088 )

♀ • 8 week old tamoxifen-treated mice exhibit increased intestinal erosion and necrosis compared with wild-type mice

growth/size/body

decreased body weight ( J:298088 )

♀ • in tamoxifen-treated mice

hematopoietic system

hematopoietic system phenotype ( J:298088 )

♀ • tamoxifen-treated mice exhibit normal adult hematopoiesis

abnormal hematopoietic stem cell physiology ( J:298088 )

♀ • enhanced self-renewal in cells from tamoxifen-treated mice

neoplasm

neoplasm ( J:298088 )

♀ • tamoxifen-treated mice do not exhibit increased spontaneous tumors

Genotype
MGI:6510523

cn17

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Rpl11^tm1.1Srn/Rpl11⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1

hematopoietic system

abnormal erythropoiesis ( J:292575 )

• tamoxifen-treated mice show defective erythropoiesis, with bone marrow showing an increase in the percentage of primitive progenitors and proerythroblasts (RI cells) and a decrease in the more matured stages (RIII, RIV, and RV cells)

• fetal livers from tamoxifen-treated pregnant mothers show an increase in the percentage of primitive progenitors and proerythroblasts (RI cells) and a decrease in the more matured stages (RIII, RIV, and RV cells)

• bone marrow of transplanted SCID mice show an increase in the percentage of primitive progenitors and proerythroblasts (RI cells) and a decrease in the more matured stages (RIII, RIV, and RV)

• fetal liver erythroid progenitors from tamoxifen-treated pregnant mothers show lower proliferation (increase in cells in G1 and a tendency of decrease in cells in S phase)

anemia ( J:292575 )

• tamoxifen-treated mice develop anemia

• mice irradiated with a single dose of gamma-radiation and treated with tamoxifen 1 week later develop anemia

abnormal proerythroblast morphology ( J:292575 )

• bone marrow of tamoxifen-treated mice shows an increase in the percentage of primitive progenitors and proerythroblasts (RI cells)

• bone marrow of transplanted SCID mice show an increase in the percentage of primitive progenitors and proerythroblasts (RI cells)

decreased erythroblast number ( J:292575 )

• bone marrow shows a decrease in the number of erythroblasts in tamoxifen-treated mice

• mutant bone marrow transplanted SCID mice show a severe decrease in erythroblasts

• however, the bone marrow is histologically normocellular and has normal ratios of hematopoietic stem cells and progenitor cells

decreased erythrocyte cell number ( J:292575 )

• mice fed a tamoxifen diet starting at 1.5-2 months of age exhibit lower red blood cell levels which becomes more pronounced with age

• mutant bone marrow transplanted SCID mice show reduced red blood cell levels over time

decreased hemoglobin content ( J:292575 )

• mutant bone marrow transplanted SCID mice show decreased hemoglobin levels over time

macrocytosis ( J:292575 )

• tamoxifen-treated mice exhibit macrocytosis which becomes more pronounced with age

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:292575 )

• gamma-irradiated mice treated with tamoxifen die earlier than controls

mortality/aging

increased mortality induced by gamma-irradiation ( J:292575 )

• gamma-irradiated mice treated with tamoxifen die earlier than controls

neoplasm

increased incidence of tumors by ionizing radiation induction ( J:292575 )

• gamma-irradiated mice treated with tamoxifen develop lymphomas, particularly in the thymus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Diamond-Blackfan anemia 7		DOID:0111878	OMIM:612562	J:292575

Genotype
MGI:6510297

cn18

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Rpl11^tm1.1Srn/Rpl11^tm1.1Srn
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1

mortality/aging

premature death ( J:292575 )

• mice treated with tamoxifen starting at 1.5 months of age show lethality, with no mice surviving beyond 8 weeks of tamoxifen treatment

digestive/alimentary system

abnormal intestine morphology ( J:292575 )

• tamoxifen-treated mice show intestinal atrophy

hematopoietic system

anemia ( J:292575 )

• at time of death, tamoxifen-treated mice show signs of developing anemia, including a pronounced decrease in bone marrow erythroblasts and an accumulation of hemosiderin in the spleen and iron in the liver

abnormal bone marrow cell morphology/development ( J:292575 )

• tamoxifen-treated mice show bone marrow aplasia

decreased erythroblast number ( J:292575 )

• tamoxifen-treated mice show a decrease in bone marrow erythroblasts at time of death

homeostasis/metabolism

increased liver iron level ( J:292575 )

• tamoxifen-treated mice show an accumulation of iron in the liver at time of death

liver/biliary system

increased liver iron level ( J:292575 )

• tamoxifen-treated mice show an accumulation of iron in the liver at time of death

Genotype
MGI:7311703

cn19

• Allelic Composition: Rad51^tm1Csha/Rad51^tm1Csha; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S/Sv * C57BL/6J

reproductive system

decreased male germ cell number ( J:324159 )

♂ • at P70, no PLZF+ spermatogonial stem cells (SSCs) are detected in the seminiferous tubules of tamoxifen-treated mice

♂ • at P14, no pachytene spermatocytes are detected in the tubules of tamoxifen-treated mice

increased male germ cell apoptosis ( J:324159 )

♂ • at P14 and P70, the number of TUNEL+ apoptotic spermatocytes in the seminiferous tubules of tamoxifen-treated mice is significantly higher than in control males

small testis ( J:324159 )

♂ • at P70, tamoxifen-treated mice show a significantly smaller testis size than control males

decreased testis weight ( J:324159 )

♂ • at P70, testis weight in tamoxifen-treated mice is 80% of that in control males

abnormal spermatogenesis ( J:324159 )

♂ • tamoxifen-treated males exhibit early spermatogenic cells loss and apoptosis

abnormal spermatocyte morphology ( J:324159 )

♂ • at P14, no pachytene spermatocytes are detected in the seminiferous tubules of tamoxifen-treated mice

♂ • at P70, chromosome spreads from tamoxifen-treated testes show a significant decrease in leptotene, zygotene and pachytene spermatocytes with a concomitant increase in diplotene and metaphase I cells relative to control testes

♂ • at P70, % of pachytene spermatocytes is significantly lower than in control testes (12.57% versus 41.37%) whereas % of diplotene spermatocytes is significantly increased (82.74% versus 48.83%)

abnormal male meiosis ( J:324159 )

♂ • at P14, no meiotic cells are found in the testes of tamoxifen-treated mice; only mitotic cells are observed

♂ • no SYCP3+ or gammaH2AX+ cells are observed in the seminiferous tubules of tamoxifen-treated mice at P14

♂ • at P70, chromosome spreads from tamoxifen-treated testes show meiosis defects, including a significant reduction in zygotene and pachytene spermatocytes, defective double-strand DNA repair, and a significant decrease in MLH1 foci in pachytene spermatocytes indicating reduced crossover formation

cellular

abnormal spermatocyte morphology ( J:324159 )

♂ • at P14, no pachytene spermatocytes are detected in the seminiferous tubules of tamoxifen-treated mice

♂ • at P70, chromosome spreads from tamoxifen-treated testes show a significant decrease in leptotene, zygotene and pachytene spermatocytes with a concomitant increase in diplotene and metaphase I cells relative to control testes

♂ • at P70, % of pachytene spermatocytes is significantly lower than in control testes (12.57% versus 41.37%) whereas % of diplotene spermatocytes is significantly increased (82.74% versus 48.83%)

decreased male germ cell number ( J:324159 )

♂ • at P70, no PLZF+ spermatogonial stem cells (SSCs) are detected in the seminiferous tubules of tamoxifen-treated mice

♂ • at P14, no pachytene spermatocytes are detected in the tubules of tamoxifen-treated mice

abnormal male meiosis ( J:324159 )

♂ • at P14, no meiotic cells are found in the testes of tamoxifen-treated mice; only mitotic cells are observed

♂ • no SYCP3+ or gammaH2AX+ cells are observed in the seminiferous tubules of tamoxifen-treated mice at P14

♂ • at P70, chromosome spreads from tamoxifen-treated testes show meiosis defects, including a significant reduction in zygotene and pachytene spermatocytes, defective double-strand DNA repair, and a significant decrease in MLH1 foci in pachytene spermatocytes indicating reduced crossover formation

increased male germ cell apoptosis ( J:324159 )

♂ • at P14 and P70, the number of TUNEL+ apoptotic spermatocytes in the seminiferous tubules of tamoxifen-treated mice is significantly higher than in control males

abnormal double-strand DNA break repair ( J:324159 )

♂ • at P70, chromosome spreads from tamoxifen-treated testes show abnormal accumulation of gammaH2AX foci on the axes of autosomal chromosomes as well as a significant increase of DMC1 foci in pachytene spermatocytes, indicating an increased incidence of unrepaired DNA breaks

homeostasis/metabolism

abnormal double-strand DNA break repair ( J:324159 )

♂ • at P70, chromosome spreads from tamoxifen-treated testes show abnormal accumulation of gammaH2AX foci on the axes of autosomal chromosomes as well as a significant increase of DMC1 foci in pachytene spermatocytes, indicating an increased incidence of unrepaired DNA breaks

endocrine/exocrine glands

small testis ( J:324159 )

♂ • at P70, tamoxifen-treated mice show a significantly smaller testis size than control males

decreased testis weight ( J:324159 )

♂ • at P70, testis weight in tamoxifen-treated mice is 80% of that in control males

Genotype
MGI:5494567

cn20

• Allelic Composition: Fto^tm1.1Rdc/Fto^tm1.1Rdc; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

premature death ( J:194922 )

• 3 of 25 mice die over the 14 weeks after tamoxifen treatment compared with 1 control mouse

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:194922 )

♂N • tamoxifen-treated male mice exhibit normal oxygen consumption and energy expenditure

decreased carbon dioxide production ( J:194922 )

♂ • in tamoxifen-treated male mice during the light and dark phases when adjusted for lean body mass

decreased respiratory quotient ( J:194922 )

♂ • in tamoxifen-treated male mice during the light and dark

growth/size/body

decreased lean body mass ( J:194922 )

♂ • in tamoxifen-treated male mice at 9 and 20 weeks

decreased body weight ( J:194922 )

♂ • in tamoxifen-treated male mice at 20 weeks

adipose tissue

increased total body fat amount ( J:194922 )

♂ • in tamoxifen-treated male mice at 20 weeks

Genotype
MGI:5440735

cn21

• Allelic Composition: Wnt5a^tm1.1Tpy/Wnt5a^tm1.1Tpy; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6

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:3717476

cn22

• Allelic Composition: Atr^tm1Bal/Atr^tm2Bal; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6

growth/size/body

decreased body weight ( J:123200 )

• 1 year after tamoxifen treatment, treated mice show a 20% decrease in body weigh compared to controls (21.3 g vs 26.6 g in controls)

pigmentation

abnormal coat/hair pigmentation ( J:123200 )

• when mice are treated with tamoxifen at 8-12 weeks of age, within 3-4 months pervasive graying of the coat is observed; no obvious phenotype is observed in controls

skeleton

kyphosis ( J:123200 )

• between 3 and 12 months after tamoxifen treatment, mice show significant kyphosis relative to control mice

decreased compact bone thickness ( J:123200 )

• 1 year after tamoxifen treatment, mice show an 18% decrease in cortical bone cross-sectional area as determined by micro-CT

abnormal trabecular bone morphology ( J:123200 )

• 1 year after tamoxifen treatment, mice show a 46-76% reduction in trabecular bone volume as determined by micro-CT

osteoporosis ( J:123200 )

• after tamoxifen treatment, mice begin to develop osteoporosis

endocrine/exocrine glands

decreased thymocyte number ( J:123200 )

• by 1-2 weeks after tamoxifen treatment, relative to controls, mice show marked suppression of thymocyte numbers which recover by 3-4 months after treatment; 6-7 months after treatment, numbers are significantly decreased again relative to controls

sebaceous gland hyperplasia ( J:123200 )

• hair follicles often display sebaceous gland cell hyperplasia

abnormal thymus involution ( J:123200 )

• mice display premature thymic involution (~1 year) after tamoxifen treatment

hematopoietic system

decreased thymocyte number ( J:123200 )

• by 1-2 weeks after tamoxifen treatment, relative to controls, mice show marked suppression of thymocyte numbers which recover by 3-4 months after treatment; 6-7 months after treatment, numbers are significantly decreased again relative to controls

abnormal thymus involution ( J:123200 )

• mice display premature thymic involution (~1 year) after tamoxifen treatment

immune system

decreased thymocyte number ( J:123200 )

• by 1-2 weeks after tamoxifen treatment, relative to controls, mice show marked suppression of thymocyte numbers which recover by 3-4 months after treatment; 6-7 months after treatment, numbers are significantly decreased again relative to controls

abnormal thymus involution ( J:123200 )

• mice display premature thymic involution (~1 year) after tamoxifen treatment

kidney inflammation ( J:123200 )

• leukocyte infiltration of the kidneys is observed in all tamoxifen-treated mice at 1 year post-treatment

liver/biliary system

abnormal liver morphology ( J:123200 )

• a significant increase in senescence-associated betagalactosidase-positive cells is observed in the liver 1 year after tamoxifen treatment

renal/urinary system

kidney inflammation ( J:123200 )

• leukocyte infiltration of the kidneys is observed in all tamoxifen-treated mice at 1 year post-treatment

kidney atrophy ( J:123200 )

• by 1 year after tamoxifen treatment, kidneys display atrophy

renal glomerulus atrophy ( J:123200 )

• glomerular degeneration in all kidneys of tamoxifen-treated mice at 1 year after treatment, but not in controls

renal tubule atrophy ( J:123200 )

• tubular degeneration in all kidneys of tamoxifen-treated mice at 1 year after treatment

renal fibrosis ( J:123200 )

• fibrotic tissue accumulates in kidneys of tamoxifen-treated mice with age

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:123200 )

• 1 week after tamoxifen treatment, ~80% of villus epithelium is lost, but recovers fully by 1 months after treatment

cardiovascular system

cardiac fibrosis ( J:123200 )

• compared to control mice, fibrotic tissue accumulates in hearts of tamoxifen-treated mice with age

adipose tissue

decreased subcutaneous adipose tissue amount ( J:123200 )

• layer is reduced up to 70% in thickness 3-6 months after tamoxifen treatment

cellular

decreased cell proliferation ( J:123200 )

• temporary loss of proliferating cells after tamoxifen treatment is observed in intestine, skin, kidney and liver

integument

decreased subcutaneous adipose tissue amount ( J:123200 )

• layer is reduced up to 70% in thickness 3-6 months after tamoxifen treatment

sebaceous gland hyperplasia ( J:123200 )

• hair follicles often display sebaceous gland cell hyperplasia

abnormal coat/hair pigmentation ( J:123200 )

• when mice are treated with tamoxifen at 8-12 weeks of age, within 3-4 months pervasive graying of the coat is observed; no obvious phenotype is observed in controls

abnormal hair growth ( J:123200 )

• after a third round of depilation, hair regrowth does not occur or regrows predominantly gray

alopecia ( J:123200 )

• when mice are treated with tamoxifen at 8-12 weeks of age, a progressive alopecia develops within 3-4 months, increasing in expressivity past 1 year of age

• single topical doses of 4-hydroxytamoxifen to skin causes alopecia and gray hair regrowth

abnormal hair shaft morphology ( J:123200 )

• remaining follicles in mice >6 months display gray shafts

• after depilation in tamoxifen-treated mice, hair shaft generation is delayed and compromised in abundance and quality

abnormal hair follicle morphology ( J:123200 )

• remaining hair follicles often show abnormal architecture with degeneration of dermal and epidermal structures

abnormal hair follicle development ( J:123200 )

• significantly delayed after tamoxifen treatment

• development is delayed in anagen after tamoxifen treatment

decreased hair follicle number ( J:123200 )

• loss of hair follicles is observed 3-6 months after tamoxifen treatment

abnormal hair cycle ( J:123200 )

• following depilation in tamoxifen-treated mice, anagen phase is accompanied by widespread degenerative follicles 4 days after depilation and delay in anagen progression 8 days after depilation

• after a second round of depilation in telogen phase, hair regrowth is more sparse, with increased representation of gray hair shafts

delayed hair regrowth ( J:123200 )

• after a second round of depilation in telogen phase, hair regrowth is more sparse, with increased representation of gray hair shafts

thick skin ( J:123200 )

• mice develop thickened epidermis 3-6 months after tamoxifen treatment

Genotype
MGI:5582193

cn23

• Allelic Composition: Col1a1^{tm3(CAG-IDH2*R140Q)Kkw}/Col1a1⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * BALB/c * C57BL/6

mortality/aging

premature death ( J:209629 )

• mean survival after tamoxifen administration is 7 weeks

respiratory system

respiratory distress ( J:209629 )

• mice show shortness of breath within 3-4 weeks of tamoxifen administration

behavior/neurological

lethargy ( J:209629 )

• mice show signs of lethargy within 3-4 weeks of tamoxifen administration

cardiovascular system

blood vessel congestion ( J:209629 )

• microscopic signs of circulatory congestion associated with cardiac failure are seen after tamoxifen administration

abnormal myocardial fiber morphology ( J:209629 )

• myocyte dropout associated with myocyte hypertrophy and nuclear enlargement 4 weeks after tamoxifen administration

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administration, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

enlarged heart ( J:209629 )

• heart enlargement after tamoxifen administration

cardiac fibrosis ( J:209629 )

• seen after tamoxifen treatment

dilated cardiomyopathy ( J:209629 )

• 4 weeks after tamoxifen administration, mice exhibit end-stage cardiomyopathy characterized by severely decreased wall motion and increased dilatation without a change in heart rate

• 4 weeks after tamoxifen administration, mice show scarring of the hearts associated with accumulating collagen deposits

decreased cardiac muscle contractility ( J:209629 )

• fractional shortening is decreased in tamoxifen treated mice

cellular

abnormal mitochondrial morphology ( J:209629 )

• evidence of mitophagy is seen in tamoxifen treated mice, as indicated by the presence of double-membrane autophagosomes

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal mitochondrial crista morphology ( J:209629 )

• disrupted cristae in cardiomyocytes of tamoxifen administration

abnormal skeletal muscle fiber mitochondrial morphology ( J:209629 )

• skeletal muscle shows abnormalities in mitochondria after tamoxifen administration

decreased mitochondrial number ( J:209629 )

• in cardiomyocytes of tamoxifen treated mice

increased cardiomyocyte apoptosis ( J:209629 )

• cardiac defects following tamoxifen administration are associated with high levels of apoptosis in cardiomyocytes

abnormal mitochondrial physiology ( J:209629 )

• decrease in the steady-state mitochondrial tricarboxylic acid cycle intermediates in mice treated with tamoxifen

homeostasis/metabolism

increased skeletal muscle glycogen level ( J:209629 )

• skeletal muscle shows glycogen accumulation in tamoxifen treated mice

nervous system

brain vacuoles ( J:209629 )

• mice treated with tamoxifen exhibit vacuoles in multiple brain regions, including cortex, white matter, hippocampus, and brain stem

• vacuoles are filled with membranous debris at both myelinated axons and nonmyelinated naked axons but not in the neuron bodies

neurodegeneration ( J:209629 )

• diffuse vacuolar leukoencephalopathy in the white and gray matter throughout the CNS of tamoxifen treated mice

• vesicles are double-membraned, suggesting elevation in autophagy and mitochondrial abnormalities in axons of the brain

• however, no evidence of apoptosis or glycogen accumulation is seen in the brain

muscle

abnormal myocardial fiber morphology ( J:209629 )

• myocyte dropout associated with myocyte hypertrophy and nuclear enlargement 4 weeks after tamoxifen administration

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administration, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

dilated cardiomyopathy ( J:209629 )

• 4 weeks after tamoxifen administration, mice exhibit end-stage cardiomyopathy characterized by severely decreased wall motion and increased dilatation without a change in heart rate

• 4 weeks after tamoxifen administration, mice show scarring of the hearts associated with accumulating collagen deposits

decreased cardiac muscle contractility ( J:209629 )

• fractional shortening is decreased in tamoxifen treated mice

increased cardiomyocyte apoptosis ( J:209629 )

• cardiac defects following tamoxifen administration are associated with high levels of apoptosis in cardiomyocytes

abnormal sarcomere morphology ( J:209629 )

• cardiomyocytes show sarcomere degeneration and severe disorganization at 4 weeks after tamoxifen administration

• skeletal muscle shows abnormalities in sarcomere organization after tamoxifen administration

abnormal Z line morphology ( J:209629 )

• cardiac Z disks are perturbed in mice treated with tamoxifen

abnormal skeletal muscle morphology ( J:209629 )

• skeletal muscle shows abnormalities in sarcomere organization, mitochondria, and glycogen accumulation in tamoxifen treated mice

abnormal skeletal muscle fiber mitochondrial morphology ( J:209629 )

• skeletal muscle shows abnormalities in mitochondria after tamoxifen administration

increased skeletal muscle glycogen level ( J:209629 )

• skeletal muscle shows glycogen accumulation in tamoxifen treated mice

growth/size/body

enlarged heart ( J:209629 )

• heart enlargement after tamoxifen administration

Genotype
MGI:5582235

cn24

• Allelic Composition: Col1a1^{tm2(CAG-IDH2*R172K)Kkw}/Col1a1⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * BALB/c * C57BL/6

mortality/aging

premature death ( J:209629 )

• mean survival after tamoxifen administration is 4 weeks

respiratory system

respiratory distress ( J:209629 )

• mice show shortness of breath within 3-4 weeks of tamoxifen administration

behavior/neurological

lethargy ( J:209629 )

• mice show signs of lethargy within 3-4 weeks of tamoxifen administration

cardiovascular system

blood vessel congestion ( J:209629 )

• microscopic signs of circulatory congestion associated with cardiac failure are seen after tamoxifen administration

increased cardiac muscle glycogen level ( J:209629 )

• cardiac muscle shows glycogen accumulation in tamoxifen treated mice

abnormal myocardial fiber morphology ( J:209629 )

• myocyte dropout associated with myocyte hypertrophy and nuclear enlargement 4 weeks after tamoxifen administration

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administration, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

enlarged heart ( J:209629 )

• heart enlargement after tamoxifen administration

cardiac fibrosis ( J:209629 )

• seen after tamoxifen treatment

dilated cardiomyopathy ( J:209629 )

• 4 weeks after tamoxifen administration, mice exhibit end-stage cardiomyopathy characterized by severely decreased wall motion and increased dilatation without a change in heart rate

• 4 weeks after tamoxifen administration, mice show scarring of the hearts associated with accumulating collagen deposits

decreased cardiac muscle contractility ( J:209629 )

• fractional shortening is decreased in tamoxifen treated mice

cellular

abnormal mitochondrial morphology ( J:209629 )

• evidence of mitophagy is seen in tamoxifen treated mice, as indicated by the presence of double-membrane autophagosomes

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal mitochondrial crista morphology ( J:209629 )

• disrupted cristae in cardiomyocytes of tamoxifen treated mice

abnormal skeletal muscle fiber mitochondrial morphology ( J:209629 )

• skeletal muscle shows abnormalities in mitochondria after tamoxifen administration

decreased mitochondrial number ( J:209629 )

• in cardiomyocytes of tamoxifen treated mice

increased cardiomyocyte apoptosis ( J:209629 )

• cardiac defects in tamoxifen treated mice are associated with high levels of apoptosis in cardiomyocytes

abnormal mitochondrial physiology ( J:209629 )

• decrease in the steady-state mitochondrial TCA cycle intermediates in mice treated with tamoxifen

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:209629 )

• cardiac muscle shows glycogen accumulation in tamoxifen treated mice

increased skeletal muscle glycogen level ( J:209629 )

• skeletal muscle shows glycogen accumulation in tamoxifen treated mice

muscle

increased cardiac muscle glycogen level ( J:209629 )

• cardiac muscle shows glycogen accumulation in tamoxifen treated mice

abnormal myocardial fiber morphology ( J:209629 )

• myocyte dropout associated with myocyte hypertrophy and nuclear enlargement 4 weeks after tamoxifen administration

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administration, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

abnormal myocardial fiber mitochondrial morphology ( J:209629 )

• mitochondrial abnormalities in cardiomyocytes after tamoxifen administraton, with disrupted cristae, smaller or swollen mitochondria, and decrease in the total mitochondrial counts and mitochondrial DNA content

dilated cardiomyopathy ( J:209629 )

• 4 weeks after tamoxifen administration, mice exhibit end-stage cardiomyopathy characterized by severely decreased wall motion and increased dilatation without a change in heart rate

• 4 weeks after tamoxifen administration, mice show scarring of the hearts associated with accumulating collagen deposits

decreased cardiac muscle contractility ( J:209629 )

• fractional shortening is decreased in tamoxifen treated mice

increased cardiomyocyte apoptosis ( J:209629 )

• cardiac defects in tamoxifen treated mice are associated with high levels of apoptosis in cardiomyocytes

abnormal sarcomere morphology ( J:209629 )

• cardiomyocytes show sarcomere degeneration and severe disorganization at 4 weeks after tamoxifen administration

• skeletal muscle shows abnormalities in sarcomere organization after tamoxifen administration

abnormal Z line morphology ( J:209629 )

• cardiac Z disks are perturbed in mice treated with tamoxifen

abnormal skeletal muscle morphology ( J:209629 )

• skeletal muscle shows abnormalities in sarcomere organization, mitochondria, and glycogen accumulation in tamoxifen treated mice

abnormal skeletal muscle fiber mitochondrial morphology ( J:209629 )

• skeletal muscle shows abnormalities in mitochondria after tamoxifen administration

increased skeletal muscle glycogen level ( J:209629 )

• skeletal muscle shows glycogen accumulation in tamoxifen treated mice

skeletal muscle fiber degeneration ( J:209629 )

• myofiber regeneration and degeneration are seen following tamoxifen administration

skeletal muscle fiber necrosis ( J:209629 )

• seen following tamoxifen administration

skeletal muscle endomysial fibrosis ( J:209629 )

• seen following tamoxifen administration

nervous system

brain vacuoles ( J:209629 )

• mice treated with tamoxifen exhibit vacuoles in multiple brain regions, including cortex, white matter, hippocampus, and brain stem

• vacuoles are filled with membranous debris at both myelinated axons and nonmyelinated naked axons but not in the neuron bodies

neurodegeneration ( J:209629 )

• diffuse vacuolar leukoencephalopathy in the white and gray matter throughout the CNS of tamoxifen treated mice

• vesicles are double-membraned, suggesting elevation in autophagy and mitochondrial abnormalities in axons of the brain

• however, no evidence of apoptosis or glycogen accumulation is seen in the brain

growth/size/body

enlarged heart ( J:209629 )

• heart enlargement after tamoxifen administration

Genotype
MGI:6236293

cn25

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Rraga^tm2Dmsa/Rraga^tm2Dmsa
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:213516 )

• over 50% of mice die within 2-3 weeks after the start of tamoxifen treatment

digestive/alimentary system

abnormal intestine apoptosis ( J:213516 )

• frequent apoptotic figures in small intestine after tamoxifen treatment

• small intestinal atrophy

growth/size/body

weight loss ( J:213516 )

• transiently lose about 20% of body weight within 1 week of tamoxifen injection

enlarged spleen ( J:213516 )

immune system

enlarged spleen ( J:213516 )

myeloid hyperplasia ( J:213516 )

• expansion of myeloid cells spreads to peripheral tissues in mice that survive more than 2 weeks after tamoxifen treatment

decreased B cell number ( J:213516 )

• expansion of monocytes is accompanied by profound reduction in B lymphocytes and/or their progenitors

increased monocyte cell number ( J:213516 )

• accumulation of monocytes in the spleen and bone marrow

neoplasm

increased lymphoma incidence ( J:213516 )

• expansion of myeloid cells is histopathologically reminiscent of histiocytic sarcoma

cellular

abnormal intestine apoptosis ( J:213516 )

• frequent apoptotic figures in small intestine after tamoxifen treatment

• small intestinal atrophy

increased apoptosis ( J:213516 )

• frequent apoptotic figures in small intestine after tamoxifen treatment

hematopoietic system

enlarged spleen ( J:213516 )

myeloid hyperplasia ( J:213516 )

• expansion of myeloid cells spreads to peripheral tissues in mice that survive more than 2 weeks after tamoxifen treatment

decreased B cell number ( J:213516 )

• expansion of monocytes is accompanied by profound reduction in B lymphocytes and/or their progenitors

increased monocyte cell number ( J:213516 )

• accumulation of monocytes in the spleen and bone marrow

Genotype
MGI:5519073

cn26

• Allelic Composition: Lin28b^tm1Gqda/Lin28b^tm1.1Gqda; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * C57BL/6

growth/size/body

growth/size/body region phenotype ( J:199720 )

N • mice exhibit normal growth when treated with tamoxifen at 7 to 9 days or 6 weeks of age

decreased body size ( J:199720 )

♂ • postnatal dwarfism in male, but not female, mice treated with tamoxifen at E15.5

Genotype
MGI:5519072

cn27

• Allelic Composition: Lin28a^tm1Gqda/Lin28a^tm1.1Gqda; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * FVB/N

growth/size/body

growth/size/body region phenotype ( J:199720 )

N • mice exhibit normal growth when treated with tamoxifen at 7 to 9 days or 6 weeks of age

decreased body size ( J:199720 )

♂ • dwarfism in male mice treated with tamoxifen at E15.5, but not as severe as in Lin28a^tm1.1Gqda homozygotes

♂ • however, female mice exhibit normal growth

decreased body length ( J:199720 )

♂ • dwarfism in male mice treated with tamoxifen at E15.5

♂ • however, female mice exhibit normal growth

Genotype
MGI:4818647

cn28

• Allelic Composition: Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺; Ndufs4^tm1Rpa/Ndufs4^tm1Rpa; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6

behavior/neurological

limb grasping ( J:161393 )

• in some mice 7 months after tamoxifen treatment

impaired coordination ( J:161393 )

• 7 months after tamoxifen treatment

decreased locomotor activity ( J:161393 )

• 7 months after tamoxifen treatment

respiratory system

respiratory distress ( J:161393 )

• in some mice 7 months after tamoxifen treatment

Genotype
MGI:5448154

cn29

• Allelic Composition: Foxo1^tm1Flv/Foxo1^tm1Flv; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6

immune system

increased interferon-gamma secretion ( J:189962 )

• regulatory T cells from tamoxifen-treated mice under the condition of IL12 and IFN-gamma stimulation unlike wild-type cells

• however, production in CD4+ T cells is normal

Genotype
MGI:5693162

cn30

• Allelic Composition: Bmp1^tm1.1Dgr/Bmp1^tm1.1Dgr; Tll1^tm2.1Dgr/Tll1^tm2.1Dgr; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6 * SJL

growth/size/body

decreased body size ( J:210366 )

• at 17 weeks of age, postnatally tamoxifen-treated mice are runted relative to control littermates

slow postnatal weight gain ( J:210366 )

• tamoxifen-treated mice exhibit reduced weight gain, so that by 17 weeks of age (11 weeks after the final tamoxifen injection), they are significantly smaller, with an average weight 73% of controls

• difference in weight is partly due to a reduction in adipose tissue

decreased body length ( J:210366 )

• at 17 weeks of age, tamoxifen-treated mice show a 13% reduction in total body length (nose to anus)

skeleton

increased osteoclast cell number ( J:210366 )

• TRAP staining revealed a sharp increase in numbers of osteoclasts lining bone surfaces in both trabecular and cortical bone of femurs in tamoxifen-treated mice relative to controls

• osteoclasts adjacent to mineralizing surfaces are ~4-fold higher than in control bone, whereas osteoclasts adjacent to non-mineralizing surfaces are not significantly altered

abnormal femur morphology ( J:210366 )

• X-ray analysis of femora showed signs of spontaneous fractures, thinned cortical bone, increased amounts of trabecular bone and, in some cases, flaring of the distal femur in tamoxifen-treated mice

• ~2/3 of distal femora exhibit some degree of flaring

decreased femur compact bone thickness ( J:210366 )

• femora of tamoxifen-treated mice exhibit highly thinned cortical bone

• m-CT analysis of femoral diaphyses showed a significantly smaller total volume (TV) and bone volume (BV), confirming that cortical bone in this region is thinner in tamoxifen-treated mice than in controls

abnormal trochanter morphology ( J:210366 )

• enlargement of the third trochanter, the attachment site for the ascending tendon of the gluteus maximus muscle, is noted in tamoxifen-treated mice at 17 weeks of age

short femur ( J:210366 )

• at 17 weeks of age, tamoxifen-treated mice show a 5% reduction in femur length

femur fracture ( J:210366 )

• X-ray analysis of femora showed signs of spontaneous fractures

abnormal tibia morphology ( J:210366 )

• flaring of the proximal tibia is observed in some tamoxifen-treated mice

abnormal tendon collagen fibril morphology ( J:210366 )

• tamoxifen-treated mice show a general shift toward larger diameter collagen fibrils in tendon

• increase in tendon fibril diameter is consistent with a significant decrease in fibril density

• however, no barb-like projections are detected on collagen fibril surfaces in tendons or bone

abnormal long bone diaphysis morphology ( J:210366 )

• microcomputed tomography (m-CT) analysis of femoral diaphyses in tamoxifen-treated mice showed that cortical bone has decreased total volume (TV) and bone volume (BV), increased porosity (BV/TV ratio) and reduced tissue mineral density (TMD), relative to controls

increased width of hypertrophic chondrocyte zone ( J:210366 )

• growth plates of tamoxifen-treated mice display mildly expanded cartilage zones

disorganized long bone epiphyseal plate ( J:210366 )

• H&E staining of femora revealed that growth plates of tamoxifen-treated mice display a mild disorganization in vertical columns

increased long bone epiphyseal plate size ( J:210366 )

• H&E staining of femora revealed that growth plates of tamoxifen-treated mice are relatively wider than in controls

abnormal long bone metaphysis morphology ( J:210366 )

• m-CT analysis of femoral metaphyses in tamoxifen-treated mice showed that trabecular bone exhibits lowered BV, BV/TV ratio, reduced trabecular bone number and increased tracecular spacing, but no significant difference in trabecular thickness or TV relative to controls

abnormal pelvic girdle bone morphology ( J:210366 )

• a 90 degree distortion of the pelvis is noted in tamoxifen-treated mice at 17 weeks of age

rib fractures ( J:210366 )

• at 17 weeks of age, tamoxifen-treated mice exhibit calluses on their ribs; some calluses contain cartilaginous cores, apparently marking sites of healing of spontaneous rib fractures

kyphosis ( J:210366 )

• tamoxifen-treated mice exhibit pronounced kyphosis at 4 months of age

• kyphosis becomes even more severe at 6 months of age

abnormal bone marrow morphology ( J:210366 )

• H&E staining of femora revealed that tamoxifen-treated mice have significantly more adipocytes in the marrow than controls

decreased bone mineral density of femur ( J:210366 )

• in tamoxifen-treated mice, femoral cortical bone shows reduced tissue mineral density relative to controls

decreased compact bone volume ( J:210366 )

• m-CT analysis of femoral diaphyses showed a significantly smaller total volume (TV) and bone volume (BV) in tamoxifen-treated mice

abnormal osteoblast cell number ( J:210366 )

• the proportion of active osteoblasts lining labeling surfaces, at which mineral is being deposited, is markedly increased in femurs of tamoxifen-treated mice relative to controls

• in contrast, the proportion of inactive osteoblasts lining non-labeling surfaces is markedly decreased relative to controls

abnormal osteocyte morphology ( J:210366 )

• immunohistochemical staining of cortical femur showed higher levels of MEPE (a marker of both osteoblasts and osteocytes) and E-11 (a marker of early osteocytes), and lower levels of sclerostin (a marker of mature osteocytes) in tamoxifen-treated mice than in controls, suggesting a deficit in osteocyte maturation

• Goldners Masson trichrome staining of cortical bone revealed increased osteoid seams, not present in controls

• at 10 weeks of age, defective osteocyte maturation is accompanied by markedly increased beta-catenin levels, indicating induction of canonical Wnt signaling

abnormal osteocyte dendritic process morphology ( J:210366 )

• FITC staining of femoral cortical areas showed that osteocytes from tamoxifen-treated mice have reduced numbers of dendritic processes relative to control osteocytes

abnormal osteocyte lacuna morphology ( J:210366 )

• SEM analysis revealed a heterogeneous mineral distribution in femoral cortical areas and showed osteocytic lacunae to be fewer, more rounded, less spindle-shaped and larger than in controls, consistent with a maturation defect

decreased bone trabecula number ( J:210366 )

• m-CT analysis of femoral metaphyses revealed reduced trabecular bone number in tamoxifen-treated mice

increased bone trabecular spacing ( J:210366 )

• m-CT analysis of femoral metaphyses revealed increased tracecular spacing in tamoxifen-treated mice

increased trabecular bone mass ( J:210366 )

• X-ray analysis of femora revealed increased amounts of trabecular bone in tamoxifen-treated mice

abnormal enthesis morphology ( J:210366 )

• at 17 weeks of age, tamoxifen-treated mice exhibit bony protuberances on the scapulae, long bones and pelvises that correspond to enlarged entheses, at which tendons and ligaments attach to bone

abnormal osteoid morphology ( J:210366 )

• Goldners Masson trichrome staining of cortical bone revealed increased osteoid seams, not present in controls

abnormal bone mineralization ( J:210366 )

• dynamic histomorphometry of femora revealed significantly increased numbers of osteoblasts depositing mineralizing ECM within the bone of tamoxifen-treated mice than in control bone

osteomalacia ( J:210366 )

increased bone ossification ( J:210366 )

• dynamic histomorphometry revealed significantly increased labeled bone surfaces in the trabecular portion of femurs in tamoxifen-treated mice relative to controls; the bone formation rate is twice that seen in controls

increased bone resorption ( J:210366 )

• tamoxifen-treated mice show remarkably high bone turnover in an attempt to repair/replace inferior bone

decreased femur stiffness ( J:210366 )

• whole femur stiffness is significantly reduced in tamoxifen-treated mice

decreased bone strength ( J:210366 )

• three-point bending analysis of femora revealed that total displacement (total amount of bone deformation prior to fracture) as well as post-yield displacement (a measure of ductility) are markedly reduced, indicating that tamoxifen-treated femora are significantly more brittle than controls

• post-yield displacement (ductility) prior to fracture is almost absent in tamoxifen-treated femora

• analysis of tissue level biomechanics following fracture revealed a lower Young's modulus and post-yield strain, lowered toughness and yield stress, and lower maximum stress capable of causing fracture

decreased femur maximal load ( J:210366 )

• maximum load sustained prior to fracture as well as the energy necessary to fracture femora are significantly reduced, indicating that femurs of tamoxifen-treated mice are more brittle, weaker, and capable of absorbing less energy than controls

decreased femur yield load ( J:210366 )

• femur yield load (the force necessary to cause permanent bone damage) is significantly reduced in tamoxifen-treated mice

decreased energy dissipated prior to femur fracture ( J:210366 )

• the energy necessary to fracture femora is significantly reduced in tamoxifen-treated mice

fragile skeleton ( J:210366 )

• at 17 weeks of age, tamoxifen-treated mice exhibit spontaneous fractures and enlarged entheses due to substantially weakened bone, with no contribution from enlargement or strengthening of skeletal muscle

limbs/digits/tail

abnormal femur morphology ( J:210366 )

• X-ray analysis of femora showed signs of spontaneous fractures, thinned cortical bone, increased amounts of trabecular bone and, in some cases, flaring of the distal femur in tamoxifen-treated mice

• ~2/3 of distal femora exhibit some degree of flaring

decreased femur compact bone thickness ( J:210366 )

• femora of tamoxifen-treated mice exhibit highly thinned cortical bone

• m-CT analysis of femoral diaphyses showed a significantly smaller total volume (TV) and bone volume (BV), confirming that cortical bone in this region is thinner in tamoxifen-treated mice than in controls

abnormal trochanter morphology ( J:210366 )

• enlargement of the third trochanter, the attachment site for the ascending tendon of the gluteus maximus muscle, is noted in tamoxifen-treated mice at 17 weeks of age

short femur ( J:210366 )

• at 17 weeks of age, tamoxifen-treated mice show a 5% reduction in femur length

femur fracture ( J:210366 )

• X-ray analysis of femora showed signs of spontaneous fractures

abnormal tibia morphology ( J:210366 )

• flaring of the proximal tibia is observed in some tamoxifen-treated mice

muscle

abnormal tendon collagen fibril morphology ( J:210366 )

• tamoxifen-treated mice show a general shift toward larger diameter collagen fibrils in tendon

• increase in tendon fibril diameter is consistent with a significant decrease in fibril density

• however, no barb-like projections are detected on collagen fibril surfaces in tendons or bone

adipose tissue

decreased gonadal fat pad weight ( J:210366 )

• after tamoxifen treatment, both sexes show a significant reduction in gonadal fad pad weight at 17 weeks of age

decreased inguinal fat pad weight ( J:210366 )

• after tamoxifen treatment, both sexes show a significant reduction in inguinal fad pad weight at 17 weeks of age

hematopoietic system

increased osteoclast cell number ( J:210366 )

• TRAP staining revealed a sharp increase in numbers of osteoclasts lining bone surfaces in both trabecular and cortical bone of femurs in tamoxifen-treated mice relative to controls

• osteoclasts adjacent to mineralizing surfaces are ~4-fold higher than in control bone, whereas osteoclasts adjacent to non-mineralizing surfaces are not significantly altered

immune system

increased osteoclast cell number ( J:210366 )

• TRAP staining revealed a sharp increase in numbers of osteoclasts lining bone surfaces in both trabecular and cortical bone of femurs in tamoxifen-treated mice relative to controls

• osteoclasts adjacent to mineralizing surfaces are ~4-fold higher than in control bone, whereas osteoclasts adjacent to non-mineralizing surfaces are not significantly altered

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:210366 )

N • at 17 weeks of age, tamoxifen-treated mice are not rachitic and show no significant differences in serum phosphate or serum ionized calcium levels relative to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta		DOID:12347	OMIM:PS166200	J:210366

Genotype
MGI:5502766

cn31

• Allelic Composition: Sh2d1a^tm1.1Knic/Y; Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ * C57BL/6

immune system

immune system phenotype ( J:196692 )

♂N • tamoxifen-treated mice exhibit normal invariant NKT cell numbers, phenotype and in vivo responsiveness to lipid antigens

abnormal NK T cell physiology ( J:196692 )

♂ • in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells

♂ • iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells

♂ • in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells

♂ • however, iNKT cells exhibit normal trafficking to the tumor site

decreased circulating interleukin-4 level ( J:196692 )

♂ • from iNKT cells from tamoxifen-treated mice in response to EL4 targets

decreased interferon-gamma secretion ( J:196692 )

♂ • from iNKT cells from tamoxifen-treated mice in response to EL4 targets

homeostasis/metabolism

decreased circulating interleukin-4 level ( J:196692 )

♂ • from iNKT cells from tamoxifen-treated mice in response to EL4 targets

hematopoietic system

abnormal NK T cell physiology ( J:196692 )

♂ • in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells

♂ • iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells

♂ • in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells

♂ • however, iNKT cells exhibit normal trafficking to the tumor site

Genotype
MGI:5502763

cn32

• Allelic Composition: Sh2d1a^tm1.1Knic/Sh2d1a^tm1.1Knic; Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ * C57BL/6

immune system

immune system phenotype ( J:196692 )

N • tamoxifen-treated mice exhibit normal invariant NKT cell numbers, phenotype and in vivo responsiveness to lipid antigens

abnormal NK T cell physiology ( J:196692 )

• in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells

• iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells

• in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells

• however, iNKT cells exhibit normal trafficking to the tumor site

decreased circulating interleukin-4 level ( J:196692 )

• from iNKT cells from tamoxifen-treated mice in response to EL4 targets

decreased interferon-gamma secretion ( J:196692 )

• from iNKT cells from tamoxifen-treated mice in response to EL4 targets

homeostasis/metabolism

decreased circulating interleukin-4 level ( J:196692 )

• from iNKT cells from tamoxifen-treated mice in response to EL4 targets

hematopoietic system

abnormal NK T cell physiology ( J:196692 )

• in vitro TCR-induced invariant NKT (iNKT) cell cytotoxicity from tamoxifen-treated mice is impaired compared to in control cells

• iNKT cells from tamoxifen-treated mice exhibit impaired control of tumor growth in vivo compared with control cells

• in response to EL4 targets, iNKT cells from tamoxifen-treated mcie form fewer conjugates and produce reduced levels of cytokines (IFN-gamma and IL4) compared with control cells

• however, iNKT cells exhibit normal trafficking to the tumor site

Genotype
MGI:6197802

cn33

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Smo/EYFP)Amc}/Gt(ROSA)26Sor⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ * C57BL/6

respiratory system

abnormal pulmonary alveolus morphology ( J:264185 )

• tamoxifen-treated lung mesenchymal fibroblasts cocultured with isolated SFTPC+ distal alveolar stem cells results in reduced distal alveolar organoid growth

Genotype
MGI:5824114

cn34

• Allelic Composition: Fus^{tm1a(EUCOMM)Wtsi}/Fus^{tm1c(EUCOMM)Wtsi}; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C3H * C57BL/6 * C57BL/6N
• Cell Lines: EPD0667_5_C04

nervous system

nervous system phenotype ( J:232167 )

N • no significant loss of lumbar level 5 motor neurons or denervation of the tibialis anterior muscle are seen at P240

Genotype
MGI:5779542

cn35

• Allelic Composition: Igf1r^tm1Jcbr/Igf1r^tm1Jcbr; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

reproductive system

reproductive system phenotype ( J:221618 )

♂N • tamoxifen-treated mice exhibit normal testicular peritubular capsule and Leydig cells

small seminiferous tubules ( J:221618 )

♂ • in tamoxifen-treated mice

decreased testis weight ( J:221618 )

♂ • in mice treated with tamoxifen at 4 weeks

abnormal spermatogenesis ( J:221618 )

♂ • in tamoxifen-treated mice

azoospermia ( J:221618 )

♂ • in tamoxifen-treated mice

oligozoospermia ( J:221618 )

♂ • seminiferous tubules in tamoxifen-treated mice are severely depleted of germ cells, including spermatogonia, spermatocytes, and spermatids

growth/size/body

decreased body weight ( J:221618 )

♂ • beginning after a week tamoxifen treatment starting at 4 weeks

postnatal growth retardation ( J:221618 )

♂ • in mice treated with tamoxifen at 4 weeks

respiratory system

abnormal bronchiole epithelium morphology ( J:221618 )

♂ • distal bronchiolar epithelium in tamoxifen-treated mice is flatter with frequent interruptions and reduced cell height, proportion of cells with apical regions extruding into the bronchiolar lumen and nuclear density compared with control cells

abnormal pulmonary alveolar parenchyma morphology ( J:221618 )

♂ • higher cellular density in tamoxifen-treated mice without a change in apoptosis rates

liver/biliary system

increased hepatocyte proliferation ( J:221618 )

♂ • 2-3 times higher in tamoxifen-treated mice without an affect in liver cellularity density or changes in apoptosis rates compared with wild-type mice

cellular

azoospermia ( J:221618 )

♂ • in tamoxifen-treated mice

oligozoospermia ( J:221618 )

♂ • seminiferous tubules in tamoxifen-treated mice are severely depleted of germ cells, including spermatogonia, spermatocytes, and spermatids

increased hepatocyte proliferation ( J:221618 )

♂ • 2-3 times higher in tamoxifen-treated mice without an affect in liver cellularity density or changes in apoptosis rates compared with wild-type mice

endocrine/exocrine glands

small seminiferous tubules ( J:221618 )

♂ • in tamoxifen-treated mice

decreased testis weight ( J:221618 )

♂ • in mice treated with tamoxifen at 4 weeks

Genotype
MGI:6120563

cn36

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(DUX4*)Plj}/Gt(ROSA)26Sor⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

behavior/neurological

impaired righting response ( J:256652 )

• pups lose the righting reflex between 5-12 weeks of age

tremors ( J:256652 )

• between 5-12 weeks of age pups develop tremors

ataxia ( J:256652 )

• between 5-12 weeks of age pups develop progressive ataxia

seizures ( J:256652 )

• pups develop spontaneous seizures characterized by periods of wild and uncontrolled running by 12 weeks of age

immune system

enlarged lymph nodes ( J:256652 )

• swollen subiliac lymph nodes

enlarged popliteal lymph nodes ( J:256652 )

integument

alopecia ( J:256652 )

• P10 pups exhibit mild alopecia by 3 weeks, progressing to severe alopecia by 12 weeks of age

retarded hair growth ( J:256652 )

• pups exhibit delayed fur growth at P10

nervous system

seizures ( J:256652 )

• pups develop spontaneous seizures characterized by periods of wild and uncontrolled running by 12 weeks of age

skeleton

kyphosis ( J:256652 )

• between 5-12 weeks of age pups develop severe kyphosis

Genotype
MGI:6121436

cn37

• Allelic Composition: Lcn6^tm1.1Ylzh/Lcn6^tm1.1Ylzh; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

reproductive system

reproductive system phenotype ( J:256079 )

N • after tamoxifen treatment fertility was not impaired and sperm fertilization ability, motility, and capacitation were similar to controls

abnormal sperm physiology ( J:256079 )

♂ • sperm from tamoxifen treated males show elevated intracellular calcium levels

premature acrosome reaction ( J:256079 )

♂ • sperm from tamoxifen treated males show enhanced spontaneous acrosome reaction frequencies when non-capacitated or capacitated for 1 h

homeostasis/metabolism

abnormal calcium ion homeostasis ( J:256079 )

♂ • sperm from tamoxifen treated males show elevated intracellular calcium levels

Genotype
MGI:6385157

cn38

• Allelic Composition: Gm30731^tm1.1Dalm/Gm30731^tm1.1Dalm; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

nervous system

abnormal neuronal stem cell physiology ( J:281278 )

• increased neurogenesis of ventricular-subventricular zone neural stem cell cultures treated with tamoxifen with 6-fold more neurons

Genotype
MGI:6459915

cn39

• Allelic Composition: Dcp2^tm1Smoc/Dcp2^tm1Smoc; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

reproductive system

decreased male germ cell number ( J:292283 )

♂ • progressive loss with only a few elongated spermatids in tamoxifen-treated mice

increased male germ cell apoptosis ( J:292283 )

♂ • in tamoxifen-treated mice

asthenozoospermia ( J:292283 )

♂ • in tamoxifen-treated mice

decreased testis weight ( J:292283 )

♂ • in tamoxifen-treated mice

male infertility ( J:292283 )

♂ • in tamoxifen-treated mice

homeostasis/metabolism

decreased circulating testosterone level ( J:292283 )

♂ • in tamoxifen-treated mice

increased circulating follicle stimulating hormone level ( J:292283 )

♂ • in tamoxifen-treated mice

increased circulating luteinizing hormone level ( J:292283 )

♂ • in tamoxifen-treated mice

cellular

decreased male germ cell number ( J:292283 )

♂ • progressive loss with only a few elongated spermatids in tamoxifen-treated mice

increased male germ cell apoptosis ( J:292283 )

♂ • in tamoxifen-treated mice

asthenozoospermia ( J:292283 )

♂ • in tamoxifen-treated mice

endocrine/exocrine glands

decreased testis weight ( J:292283 )

♂ • in tamoxifen-treated mice

Genotype
MGI:5496426

cn40

• Allelic Composition: Gt(ROSA)26Sor^tm2Iaai/Gt(ROSA)26Sor⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

abnormal bone marrow cell physiology ( J:196407 )

• total bone marrow cells transplanted in lethally irradiated recipients and treated with tamoxifen induce aggressive T-cell acute lymphoblastic leukemia (T-ALL) resulting in death unlike control cells

Genotype
MGI:5496425

cn41

• Allelic Composition: Gt(ROSA)26Sor^tm1Iaai/Gt(ROSA)26Sor⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

abnormal bone marrow cell physiology ( J:196407 )

• total bone marrow cells transplanted in lethally irradiated recipients and treated with tamoxifen induce a low abundant transient wave of CD4/CD8 double-positive T cells without inducing acute T cell leukemia (T-ALL) compared with control cells

Genotype
MGI:5488603

cn42

• Allelic Composition: Cxcl12^tm1.1Sjm/Cxcl12^tm1.1Sjm; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/?
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

decreased bone marrow cell number ( J:194748 )

• reduced bone marrow cellularity

decreased leukocyte cell number ( J:194748 )

• white blood cell counts are significantly reduced after tamoxifen treatment

decreased lymphocyte cell number ( J:194748 )

decreased hematopoietic stem cell number ( J:194748 )

• reduced numbers of CD150+ CD480- LIN- SCA1+ cKIT+ stem cells

immune system

decreased leukocyte cell number ( J:194748 )

• white blood cell counts are significantly reduced after tamoxifen treatment

decreased lymphocyte cell number ( J:194748 )

Genotype
MGI:5449733

cn43

• Allelic Composition: Il2^tm1.1Kasm/Il2^tm1.1Kasm; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/?
• Genetic Background: involves: 129S/SvEv * C57BL/6

immune system

immune system phenotype ( J:190168 )

N • normal increase in size and granularity of both CD4+ and CD8+ T cells after 5 days of tamoxifen treatment and activation with anti-CD3/28

N • also normal increase in DNA replication in activated CD4+ and CD8+ T cells after 5 days of tamoxifen treatment and activation with anti-CD3/28

decreased circulating interleukin-17 level ( J:190168 )

• after 5 days of tamoxifen treatment and activation with anti-CD3/28

cellular

abnormal cellular respiration ( J:190168 )

• fail to switch from oxidative phosphorylation to aerobic glycolysis after 5 days of tamoxifen treatment and activation with anti-CD3/28

homeostasis/metabolism

decreased circulating interleukin-17 level ( J:190168 )

• after 5 days of tamoxifen treatment and activation with anti-CD3/28

Genotype
MGI:7343747

cn44

• Allelic Composition: Dido1^tm3Cmar/Dido1^tm3.1Cmar; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

reproductive system

small testis ( J:328215 )

• after 35 days of tamoxifen treatment

decreased testis weight ( J:328215 )

• after 35 days of tamoxifen treatment

testis degeneration ( J:328215 )

• with partial collapse of seminiferous tubules and defective germ line maturation in tamoxifen-treated mice

male infertility ( J:328215 )

• 4 of 7 tamoxifen-treated male mice are infertile compared with 1 of 5 wild-type mice

behavior/neurological

ataxia ( J:328215 )

• progressively increasing with age in tamoxifen-treated mice

impaired coordination ( J:328215 )

• on a rotarod at three months in tamoxifen-treated mice

seizures ( J:328215 )

• in some tamoxifen-treated mice

endocrine/exocrine glands

small testis ( J:328215 )

• after 35 days of tamoxifen treatment

decreased testis weight ( J:328215 )

• after 35 days of tamoxifen treatment

testis degeneration ( J:328215 )

• with partial collapse of seminiferous tubules and defective germ line maturation in tamoxifen-treated mice

growth/size/body

decreased body weight ( J:328215 )

• reduced weight gain for 70 days following tamoxifen treatment with mice never catching up to wild-type mice

enlarged liver ( J:328215 )

• after 40-50 days of tamoxifen treatment

homeostasis/metabolism

increased circulating cholesterol level ( J:328215 )

• after 43 days of tamoxifen treatment

increased circulating alanine transaminase level ( J:328215 )

• in tamoxifen-treated mice

increased circulating aspartate transaminase level ( J:328215 )

• in tamoxifen-treated mice

liver/biliary system

enlarged liver ( J:328215 )

• after 40-50 days of tamoxifen treatment

liver inflammation ( J:328215 )

• with ballooning degeneration in the parenchyma and occasional foci of lymphocytic infiltration in tamoxifen-treated mice

abnormal hepatocyte morphology ( J:328215 )

• enlarged in tamoxifen-treated mice

increased hepatocyte karyomegaly ( J:328215 )

• in tamoxifen-treated mice

immune system

liver inflammation ( J:328215 )

• with ballooning degeneration in the parenchyma and occasional foci of lymphocytic infiltration in tamoxifen-treated mice

nervous system

seizures ( J:328215 )

• in some tamoxifen-treated mice

cellular

increased hepatocyte karyomegaly ( J:328215 )

• in tamoxifen-treated mice

Genotype
MGI:7612206

cn45

• Allelic Composition: Armcx3^tm1.1Eso/Y; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

growth/size/body

decreased susceptibility to diet-induced obesity ( J:345411 )

♂ • tamoxifen-treated mice fed a high-fat diet gain less body weight than controls

♂ • tamoxifen-treated mice injected with DEN exhibit a lower increase in body weight compared to DEN-injected controls, regardless of diet; this is due to reduced adiposity and not growth

liver/biliary system

decreased susceptibility to diet-induced hepatic steatosis ( J:345411 )

♂ • tamoxifen-treated mice are resistant to developing high-fat diet induced non-alcohol fatty liver disease

♂ • tamoxifen-treated mice, injected with DEN and fed a high-fat diet show strongly reduced hepatic steatosis

neoplasm

decreased incidence of tumors by chemical induction ( J:345411 )

♂ • mice treated with tamoxifen on days 1 to 3 after birth then injected with diethylnitrosamine (DEN) 14 days later to induce hepatic carcinogenesis and fed a high-fat diet show a decrease in liver tumor number, average tumor size and maximum tumor size compared with controls, indicating decreased susceptibility to DEN-induced tumorigenesis on a high-fat diet

♂ • tumor regions show increased hepatocyte apoptosis and a greater accumulation of macrophages than in controls

abnormal tumor morphology ( J:345411 )

♂ • a greater accumulation of macrophages is seen in tumors from high-diet fed, DEN-injected, and tamoxifen-treated mutants than in controls

♂ • tumor regions, but not non-tumor regions, from tamoxifen-treated, DEN-injected, and high-fat diet fed mice show increased hepatocyte apoptosis

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:345411 )

♂ • tamoxifen-treated mice fed a high-fat diet gain less body weight than controls

♂ • tamoxifen-treated mice injected with DEN exhibit a lower increase in body weight compared to DEN-injected controls, regardless of diet; this is due to reduced adiposity and not growth

decreased circulating glucose level ( J:345411 )

♂ • tamoxifen-treated mice, injected with DEN and fed a low-fat diet show lower glycemia than controls

increased circulating insulin level ( J:345411 )

♂ • tamoxifen-treated mice fed a low-fat diet exhibit higher insulin levels

decreased circulating alanine transaminase level ( J:345411 )

♂ • tamoxifen-treated mice fed a high-fat diet show a reduction in alanine aminotransferase (ALT) activity in plasma compared to controls, indicating reduced hepatocellular injury

♂ • tamoxifen-treated mice, injected with DEN and fed a high-fat diet show blunted ALT activity

improved glucose tolerance ( J:345411 )

♂ • tamoxifen-treated mice fed a high-fat diet exhibit improved glucose tolerance

increased insulin sensitivity ( J:345411 )

♂ • the HOMA-IR index is blunted in tamoxifen-treated mice fed a high-fat diet compared to an increase in controls

decreased incidence of tumors by chemical induction ( J:345411 )

♂ • mice treated with tamoxifen on days 1 to 3 after birth then injected with diethylnitrosamine (DEN) 14 days later to induce hepatic carcinogenesis and fed a high-fat diet show a decrease in liver tumor number, average tumor size and maximum tumor size compared with controls, indicating decreased susceptibility to DEN-induced tumorigenesis on a high-fat diet

♂ • tumor regions show increased hepatocyte apoptosis and a greater accumulation of macrophages than in controls

behavior/neurological

increased food intake ( J:345411 )

♂ • tamoxifen-treated mice fed a high-fat diet have a higher food intake than controls

adipose tissue

decreased total body fat amount ( J:345411 )

♂ • tamoxifen-treated mice injected with DEN show reduced adiposity, as seen by smaller adipose depots, regardless of diet

Genotype
MGI:5496671

cn46

• Allelic Composition: Phf2^tm1.2Yima/Phf2^tm1.2Yima; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/6J * SJL

adipose tissue

abnormal adipose tissue development ( J:198329 )

• stromal vascular cells treated with a differentiation cocktail exhibit impaired adipogenesis when treated with tamoxifen compared with control cells

Genotype
MGI:6276277

cn47

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Rnpc3^{tm1c(EUCOMM)Wtsi}/Rnpc3^{tm1c(EUCOMM)Wtsi}
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/6N
• Cell Lines: EPD0441_1_B10

mortality/aging

moribund ( J:267519 )

• at 8 days after tamoxifen (TAM) treatment, adult mice show signs of malnutrition and stress (scruffy coat, docile, and hunched behavior) requiring euthanasia

growth/size/body

weight loss ( J:267519 )

• adult mice show irreversible weight loss by 6 days after TAM treatment

behavior/neurological

hunched posture ( J:267519 )

• hunched behavior at 8 days after TAM treatment

immune system

small intestinal inflammation ( J:267519 )

• infiltration of immune cells in small intestinal epithelium at 6 days after TAM treatment

esophageal inflammation ( J:267519 )

• signs of erosive esophagitis at 8 days after TAM treatment

decreased thymus weight ( J:267519 )

• significant reduction in thymus weight at 8 days at 8 days after TAM treatment

thymus atrophy ( J:267519 )

• significantly smaller thymus with no discernible medullary or cortical regions at 8 days after TAM treatment

thymus cortex atrophy ( J:267519 )

• at 8 days after TAM treatment

thymus medulla atrophy ( J:267519 )

• at 8 days after TAM treatment

decreased leukocyte cell number ( J:267519 )

• significant leucopenia at 8 days after TAM treatment

decreased lymphocyte cell number ( J:267519 )

• significant decrease in lymphocyte number at 8 days after TAM treatment

decreased monocyte cell number ( J:267519 )

• significant decrease in monocyte number at 8 days after TAM treatment

digestive/alimentary system

increased small intestinal crypt cell apoptosis ( J:267519 )

• significant increase in the number of apoptotic cells in the highly proliferative, stem/progenitor compartment of the small intestinal crypts at 2 and 4 days after TAM treatment

abnormal enterocyte proliferation ( J:267519 )

• reduced cell proliferation in the proliferative compartment of the small intestinal epithelium at 4 days after TAM treatment

abnormal small intestinal crypt cell proliferation ( J:267519 )

• marked reduction in BrdU+ cells in small intestinal crypts at 4 days after TAM treatment

• new BrdU+ crypt-like structures corresponding to sites of regeneration at 6 and 8 days after TAM treatment

abnormal digestive system morphology ( J:267519 )

• severe atrophy of the entire gastrointestinal epithelium with mucosa disruption from the esophagus to the rectum at 8 days after TAM treatment

• extensive degeneration of the epithelial layer interspersed with discrete pockets of regenerating crypt-like structures

abnormal esophageal squamous epithelium morphology ( J:267519 )

• disrupted organization of the squamous epithelium of the esophagus at 8 days after TAM treatment

abnormal intestinal epithelium morphology ( J:267519 )

• at 8 days after TAM treatment, the epithelial monolayer lining the small intestine and colon contains vacuolated epithelial cells scattered throughout the submucosa; epithelial layer degeneration is intermixed with discrete pockets of regenerating crypt-like structures

• loss of epithelial integrity in the small intestine and colon with nuclei rounding up and cells losing apico-basal polarity at 4 days after TAM treatment

• highly disorganized small intestine epithelium, with crypt loss, decreased villus height, infiltration of immune cells, and ulceration at 6 days after TAM treatment

• thinner and flatter epithelial cells in the colon at 6 days after TAM treatment

abnormal intestinal mucosa morphology ( J:267519 )

• at 8 days after TAM treatment

abnormal large intestine crypts of Lieberkuhn morphology ( J:267519 )

• loss of crypt structure in the colon at 4 days after TAM treatment

• large vacuolated spaces in colonic crypts at 6 days after TAM treatment

abnormal small intestine crypts of Lieberkuhn morphology ( J:267519 )

• loss of crypt structure in the small intestine at 4 days after TAM treatment

decreased small intestinal villus height ( J:267519 )

• reduced villus height in the small intestine at 6 days after TAM treatment

abnormal stomach glandular epithelium morphology ( J:267519 )

• degeneration of columnar mucous epithelium of the glandular stomach at 8 days after TAM treatment

small intestinal inflammation ( J:267519 )

• infiltration of immune cells in small intestinal epithelium at 6 days after TAM treatment

esophageal inflammation ( J:267519 )

• signs of erosive esophagitis at 8 days after TAM treatment

hematopoietic system

decreased thymus weight ( J:267519 )

• significant reduction in thymus weight at 8 days at 8 days after TAM treatment

thymus atrophy ( J:267519 )

• significantly smaller thymus with no discernible medullary or cortical regions at 8 days after TAM treatment

thymus cortex atrophy ( J:267519 )

• at 8 days after TAM treatment

thymus medulla atrophy ( J:267519 )

• at 8 days after TAM treatment

anemia ( J:267519 )

• significant anemia at 8 days after TAM treatment

decreased erythrocyte cell number ( J:267519 )

• significant decrease in RBC number at 8 days after TAM treatment

thrombocytopenia ( J:267519 )

• severe thrombocytopenia at 8 days after TAM treatment

decreased leukocyte cell number ( J:267519 )

• significant leucopenia at 8 days after TAM treatment

decreased lymphocyte cell number ( J:267519 )

• significant decrease in lymphocyte number at 8 days after TAM treatment

decreased monocyte cell number ( J:267519 )

• significant decrease in monocyte number at 8 days after TAM treatment

integument

sebaceous gland atrophy ( J:267519 )

• paucity of sebaceous glands at 8 days after TAM treatment

disheveled coat ( J:267519 )

• scruffy coat at 8 days at 8 days after TAM treatment

abnormal skin morphology ( J:267519 )

• mild skin abnormalities at 8 days after TAM treatment

epidermal atrophy ( J:267519 )

• attenuated epidermis at 8 days after TAM treatment

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:267519 )

• loss of crypt structure in the colon at 4 days after TAM treatment

• large vacuolated spaces in colonic crypts at 6 days after TAM treatment

abnormal small intestine crypts of Lieberkuhn morphology ( J:267519 )

• loss of crypt structure in the small intestine at 4 days after TAM treatment

decreased thymus weight ( J:267519 )

• significant reduction in thymus weight at 8 days at 8 days after TAM treatment

thymus atrophy ( J:267519 )

• significantly smaller thymus with no discernible medullary or cortical regions at 8 days after TAM treatment

thymus cortex atrophy ( J:267519 )

• at 8 days after TAM treatment

thymus medulla atrophy ( J:267519 )

• at 8 days after TAM treatment

sebaceous gland atrophy ( J:267519 )

• paucity of sebaceous glands at 8 days after TAM treatment

cellular

increased small intestinal crypt cell apoptosis ( J:267519 )

• significant increase in the number of apoptotic cells in the highly proliferative, stem/progenitor compartment of the small intestinal crypts at 2 and 4 days after TAM treatment

abnormal enterocyte proliferation ( J:267519 )

• reduced cell proliferation in the proliferative compartment of the small intestinal epithelium at 4 days after TAM treatment

abnormal small intestinal crypt cell proliferation ( J:267519 )

• marked reduction in BrdU+ cells in small intestinal crypts at 4 days after TAM treatment

• new BrdU+ crypt-like structures corresponding to sites of regeneration at 6 and 8 days after TAM treatment

Genotype
MGI:6276274

cn48

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Rnpc3^{tm1c(EUCOMM)Wtsi}/Rnpc3⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/6N
• Cell Lines: EPD0441_1_B10

normal phenotype

no abnormal phenotype detected ( J:267519 )

• tamoxifen-treated adult mice appear phenotypically normal with no significant weight loss relative to control mice

Genotype
MGI:5749852

cn49

• Allelic Composition: Pdzrn3^tm1.1Ysa/Pdzrn3^tm1.1Ysa; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/?
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/6NCrlj * CBA/JNCrlj

mortality/aging

embryonic lethality during organogenesis ( J:222522 )

• death between E11.5 and E12.5 of embryos exposed to tamoxifen between E7.5 and E9.5

• tamoxifen exposure between E10.5 and E12.5 does not induce lethality

embryo

embryo phenotype ( J:222522 )

N • embryos exposed to tamoxifen between E7.5 and E9.5

embryonic growth retardation ( J:222522 )

• retarded growth at E9.5

abnormal extraembryonic tissue morphology ( J:222522 )

abnormal vitelline vasculature morphology ( J:222522 )

• yolk sac vascularization is altered between E9.5 and E10.5

abnormal vitelline artery morphology ( J:222522 )

• increased diameter of the vitellin artery

disorganized yolk sac vascular plexus ( J:222522 )

• disorganized vascular network by E11.5

abnormal placenta morphology ( J:222522 )

abnormal placental labyrinth vasculature morphology ( J:222522 )

• fetal capillaries do not invade the labyrinth

decreased placental labyrinth size ( J:222522 )

• reduced labyrinth layer of the placenta

cardiovascular system

abnormal brain vasculature morphology ( J:222522 )

• reduced brain vasculature at E11.5

abnormal placental labyrinth vasculature morphology ( J:222522 )

• fetal capillaries do not invade the labyrinth

abnormal vitelline vasculature morphology ( J:222522 )

• yolk sac vascularization is altered between E9.5 and E10.5

abnormal vitelline artery morphology ( J:222522 )

• increased diameter of the vitellin artery

disorganized yolk sac vascular plexus ( J:222522 )

• disorganized vascular network by E11.5

nervous system

nervous system phenotype ( J:222522 )

N • embryos exposed to tamoxifen between E7.5 and E9.5

abnormal brain vasculature morphology ( J:222522 )

• reduced brain vasculature at E11.5

growth/size/body

embryonic growth retardation ( J:222522 )

• retarded growth at E9.5

Genotype
MGI:5532734

cn50

• Allelic Composition: Nr6a1^{tm1c(EUCOMM)Wtsi}/Nr6a1^{tm1c(EUCOMM)Wtsi}; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/6N * SJL
• Cell Lines: EPD0105_6_D03

reproductive system

reproductive system phenotype ( J:204241 )

♀N • tamoxifen-treated mice exhibit normal early meiosis and oogenesis at E16.5

Genotype
MGI:5306350

cn51

• Allelic Composition: Kitl^tm2.1Sjm/Kitl^tm2.1Sjm; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/Ka * SJL

hematopoietic system

anemia ( J:180431 )

• in tamoxifen-treated mice

decreased bone marrow cell number ( J:180431 )

• bone marrow cells from tamoxifen-treated mice used to repopulate irradiated mice exhibit reduced bone marrow-derived cell production (total, myeloid, T cell, and B cell)

decreased hematopoietic cell number ( J:180431 )

• in tamoxifen-treated mice

decreased erythrocyte cell number ( J:180431 )

• in tamoxifen-treated mice

abnormal bone marrow cell physiology ( J:180431 )

• bone marrow cells from tamoxifen-treated mice used to repopulate irradiated mice exhibit reduced bone marrow-derived cell production (total, myeloid, T cell, and B cell)

liver/biliary system

liver hypoplasia ( J:180431 )

• in tamoxifen-treated mice

Genotype
MGI:4840218

cn52

• Allelic Composition: Stk11^tm1.1Sjm/Stk11^tm1.1Sjm; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

hematopoietic system

abnormal bone marrow cell physiology ( J:165090 )

• hematopoietic stem cells from doxycycline-treated mice fail to exhibit long-term reconstitution unlike wild-type cells

Genotype
MGI:5766642

cn53

• Allelic Composition: Clec16a^tm1.1Hhak/Clec16a^tm1.1Hhak; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

homeostasis/metabolism

abnormal mitophagy ( J:214528 )

• OHT-treated fibroblasts show a defect in trafficking of autophagosomes to the lysosomal compartment during late mitophagy

decreased oxygen consumption ( J:214528 )

• hydroxytamoxifen (OHT)-treated primary dermal fibroblasts exhibit a reduced oxygen consumption rate relative to controls

cellular

abnormal mitophagy ( J:214528 )

• OHT-treated fibroblasts show a defect in trafficking of autophagosomes to the lysosomal compartment during late mitophagy

Genotype
MGI:5906758

cn54

• Allelic Composition: Nsmce2^tm2.1Ofc/Nsmce2^tm2.1Ofc; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

mortality/aging

premature death ( J:227197 )

• mice die within 1 year following tamoxifen exposure at weaning

premature aging ( J:227197 )

• tamoxifen exposure beginning at weaning results in a progressive and generalized progeroid syndrome

cellular

abnormal cell nucleus morphology ( J:227197 )

• increased incidence of micronucleated cells in MEFs following tamoxifen treatment

• dramatic increase in micronuclei in proliferating tissues following tamoxifen treatment at weaning

abnormal mitosis ( J:227197 )

• tamoxifen exposure at E13.5 results in accumulation of mitotic cells in the thymus

elevated level of mitotic sister chromatid exchange ( J:227197 )

• sister chromatid exchanges and inter-telomeric recombination rates are increased in MEFs following tamoxifen treatmen

mitotic nondisjunction ( J:227197 )

• accumulation of intercellular DNA bridges in MEFs following tamoxifen treatment

adipose tissue

decreased total body fat amount ( J:227197 )

• following tamoxifen exposure at weaning

pigmentation

abnormal coat/hair pigmentation ( J:227197 )

• following tamoxifen exposure at weaning

abnormal skin pigmentation ( J:227197 )

• following tamoxifen exposure at weaning

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:227197 )

• dramatic increase in micronuclei following tamoxifen treatment at weaning

embryo

decreased embryo size ( J:227197 )

• tamoxifen exposure at E13.5 results in intrauterine dwarfism with overall loss of cellularity particularly in some specific organs including the thymus

endocrine/exocrine glands

abnormal thymus physiology ( J:227197 )

• tamoxifen exposure at E13.5 results in accumulation of mitotic cells in the thymus

growth/size/body

decreased embryo size ( J:227197 )

• tamoxifen exposure at E13.5 results in intrauterine dwarfism with overall loss of cellularity particularly in some specific organs including the thymus

hematopoietic system

abnormal thymus physiology ( J:227197 )

• tamoxifen exposure at E13.5 results in accumulation of mitotic cells in the thymus

anemia ( J:227197 )

• progressive anemia following tamoxifen exposure at weaning

immune system

abnormal thymus physiology ( J:227197 )

• tamoxifen exposure at E13.5 results in accumulation of mitotic cells in the thymus

integument

abnormal coat/hair pigmentation ( J:227197 )

• following tamoxifen exposure at weaning

abnormal skin pigmentation ( J:227197 )

• following tamoxifen exposure at weaning

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bloom syndrome		DOID:2717	OMIM:210900	J:227197

Genotype
MGI:5429245

cn55

• Allelic Composition: Cdk7^{Gt(D032B11)1.1Wrst}/Cdk7^{Gt(D032B11)1.1Wrst}; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvPas * 129S2/SvPas * C57BL/6 * SJL

mortality/aging

premature aging ( J:183925 )

• at 8 months of age in mice exposed to a tamoxifen diet from weaning

growth/size/body

weight loss ( J:183925 )

• significant weight loss at 8 months of age in mice exposed to a tamoxifen diet from weaning

digestive/alimentary system

abnormal small intestine crypts of Lieberkuhn morphology ( J:183925 )

• hypoplastic crypts at 8 months of age in mice exposed to a tamoxifen diet from weaning

decreased small intestinal villus size ( J:183925 )

• hypoplastic villi at 8 months of age in mice exposed to a tamoxifen diet from weaning

integument

decreased subcutaneous adipose tissue amount ( J:183925 )

• at 8 months of age in mice exposed to a tamoxifen diet from weaning

abnormal coat/hair pigmentation ( J:183925 )

• pervasive hair graying at 8 months of age in mice exposed to a tamoxifen diet from weaning

alopecia ( J:183925 )

• diffuse alopecia at 8 months of age in mice exposed to a tamoxifen diet from weaning

abnormal hair follicle morphology ( J:183925 )

• transformation of follicular epithelium into sebaceous glands at 8 months of age in mice exposed to a tamoxifen diet from weaning

abnormal hair follicle bulge morphology ( J:183925 )

• depletion of epithelial stem cells at 8 months of age in mice exposed to a tamoxifen diet from weaning

abnormal skin morphology ( J:183925 )

• reduction in average telomere length in skin cells at 8 months of age in mice exposed to a tamoxifen diet from weaning

thin dermal layer ( J:183925 )

• reduced dermal thickness at 8 months of age in mice exposed to a tamoxifen diet from weaning

skeleton

kyphosis ( J:183925 )

• at 8 months of age in mice exposed to a tamoxifen diet from weaning

abnormal bone marrow morphology ( J:183925 )

• some bone marrow is replaced by adipose tissue in mice at 8 months of age exposed to a tamoxifen diet from weaning

decreased bone mineral content ( J:183925 )

• at 8 months of age in mice exposed to a tamoxifen diet from weaning

decreased trabecular bone mass ( J:183925 )

• at 8 months of age in mice exposed to a tamoxifen diet from weaning

renal/urinary system

abnormal kidney morphology ( J:183925 )

• progressive nephropathy at 8 months of age in mice exposed to a tamoxifen diet from weaning

nephrocalcinosis ( J:183925 )

• severe medullary calcification at 8 months of age in mice exposed to a tamoxifen diet from weaning

hematopoietic system

decreased hematopoietic stem cell number ( J:183925 )

• at 8 months of age in mice exposed to a tamoxifen diet from weaning

pigmentation

abnormal coat/hair pigmentation ( J:183925 )

• pervasive hair graying at 8 months of age in mice exposed to a tamoxifen diet from weaning

adipose tissue

decreased subcutaneous adipose tissue amount ( J:183925 )

• at 8 months of age in mice exposed to a tamoxifen diet from weaning

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:183925 )

• hypoplastic crypts at 8 months of age in mice exposed to a tamoxifen diet from weaning

cellular

decreased telomere length ( J:183925 )

• reduction in average telomere length in skin cells at 8 months of age in mice exposed to a tamoxifen diet from weaning

Genotype
MGI:3710346

cn56

• Allelic Composition: Epas1^tm1Mcs/Epas1^tm1.1Mcs; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129X1/SvJ * FVB/N

hematopoietic system

enlarged spleen ( J:119731 )

• spleens are enlarged relative to controls (0.5% spleen weight to body weight vs. ~0.4% in controls)

anemia ( J:119731 )

• occurs after postnatal cre induction

abnormal proerythroblast morphology ( J:119731 )

• erythroid progenitors from bone marrow form ~50% fewer erythroid burst-forming units (BFU-E) and colony-forming units (CFU-E) in culture than control cells, whereas erythroid progenitors from the spleen form more BFU-E and CFU-E

• there are fewer CD71+ immature erythroid progenitors in the bone marrow, and a higher percentage of CD71+ /Ter119+ double positive cells in the spleen

decreased erythrocyte cell number ( J:119731 )

• with acute deletion of Epas1 at 6-8 weeks induced by tamoxifen administration, animals have decreased red blood cell numbers relative to controls

decreased hematocrit ( J:119731 )

• with acute deletion of Epas1 at 6-8 weeks induced by tamoxifen administration, animals have decreased hematocrit relative to controls

decreased hemoglobin content ( J:119731 )

• with acute deletion of Epas1 at 6-8 weeks induced by tamoxifen administration, animals have decreased hemoglobin levels relative to controls

reticulocytopenia ( J:119731 )

• numbers are decreased compared to controls

abnormal hematopoietic system physiology ( J:119731 )

• mice show weak induction of erythropoietin after phenylhydrazine treatment

immune system

enlarged spleen ( J:119731 )

• spleens are enlarged relative to controls (0.5% spleen weight to body weight vs. ~0.4% in controls)

growth/size/body

enlarged spleen ( J:119731 )

• spleens are enlarged relative to controls (0.5% spleen weight to body weight vs. ~0.4% in controls)

Genotype
MGI:6403623

cx57

• Allelic Composition: Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/Ndor1⁺; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N

neoplasm

tumor regression ( J:223417 )

• in tamoxifen treated mice compared with untreated mice due to increased apoptosis in tumor cells