Phenotypes associated with this allele

• Allele Symbol: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}
• Allele Name: targeted mutation 1, Tyler Jacks
• Allele ID: MGI:3699244
• Summary: 50 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^tm1(Grem1)Svok	involves: 129S1/Sv * 129S4/SvJae	MGI:5588435
cn2	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^tm1(Pyy)Paba	involves: 129S4/SvJae	MGI:5447473
cn3	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Secisbp2^tm1.1Amdu/Secisbp2^tm1.2Amdu	B6(129S4)-Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj Secisbp2^tm1.1Amdu Secisbp2^tm1.2Amdu	MGI:6323622
cn4	Gnai2^tm2.1Rneu/Gnai2^tm2.1Rneu Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	B6.Cg-Gt(ROSA)26Sor^tm1(cre/ert2)Tyj Gnai2^tm2.1Rneu	MGI:5614488
cn5	Mirc14^tm1.1Czc/Mirc14^tm1.1Czc Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	either: (involves: 129P2/OlaHsd * 129S4/SvJae * 129S4/SvJaeSor) or (involves: 129P2/OlaHsd * 129S4/SvJae * 129S4/SvJaeSor * C57BL/6)	MGI:5467841
cn6	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj Nus1^tm1.1Qrm/Nus1^tm1.1Qrm	involves: 129 * C57BL/6 * SJL	MGI:6106902
cn7	Smg6^tm1.1Zqw/Smg6^tm1.1Zqw Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:5763151
cn8	Hprt1^tm6(CAG-fat-1)Geno/Y Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:5629844
cn9	Trp53^tm1Brn/Trp53^tm1Brn Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:6695306
cn10	Trp53^tm1Brn/Trp53^+ Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:6695307
cn11	Kras^tm5Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:5007795
cn12	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Hprt1^tm6(CAG-fat-1)Geno/Hprt1^tm6(CAG-fat-1)Geno	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:5629845
cn13	Setd4^tm1c(KOMP)Wtsi/Setd4^tm1c(KOMP)Wtsi Trp53^tm1Brn/Trp53^+ Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6N	MGI:6695305
cn14	Setd4^tm1c(KOMP)Wtsi/Setd4^tm1c(KOMP)Wtsi Trp53^tm1Brn/Trp53^tm1Brn Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6N	MGI:6695303
cn15	Apoe^tm1Unc/Apoe^tm1Unc Atic^tm1c(EUCOMM)Hmgu/Atic^tm1c(EUCOMM)Hmgu Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7511828
cn16	Htatsf1^tm1Jakn/Htatsf1^tm1Jakn Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:6362663
cn17	Bmi1^tm1Sgon/Bmi1^tm1Sgon Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/?	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:5693400
cn18	Aldh1a1^tm1Gdu/Aldh1a1^tm1Gdu Aldh1a2^tm1.1Mbp/Aldh1a2^tm1.1Mbp Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:7327640
cn19	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Tacc3^tm1.1Tno/Tacc3^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:5305074
cn20	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Tacc3^tm1.1Tno/Tacc3^tm1.2Tno Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:5305073
cn21	Trp53^tm3Att/Trp53^tm3Att Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/?	involves: 129S4/SvJae	MGI:5140103
cn22	Kras^tm4Tyj/Kras^+ Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae	MGI:3776023
cn23	Trp53^tm1Att/Trp53^tm1Att Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/?	involves: 129S4/SvJae	MGI:5140097
cn24	Angpt1^tm1.1Yona/Angpt1^tm1.1Yona Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae	MGI:5585466
cn25	Trp53^tm4Att/Trp53^tm4Att Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/?	involves: 129S4/SvJae	MGI:5140099
cn26	E2f4^tm2.1Lees/E2f4^tm2.1Lees Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6	MGI:5904345
cn27	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Supt5^tm1.1Rrp/Supt5^tm1.2Rrp	involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6	MGI:6867021
cn28	Agr2^tm1Lex/Agr2^tm1Lex Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * 129S5/SvEvBrd * C57BL/6	MGI:5494478
cn29	Pde6b^atrd1/Pde6b^tm1Eye Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * 129S6/SvEvTac * BALB/cAnN * C3H/HeN * C57BL/6J	MGI:5544446
cn30	Ddrgk1^tm1c(EUCOMM)Hmgu/Ddrgk1^tm1c(EUCOMM)Hmgu Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6N	MGI:5897612
cn31	Ufl1^tm1c(EUCOMM)Wtsi/Ufl1^tm1c(EUCOMM)Wtsi Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6N	MGI:5825319
cn32	Nup160^tm1Mdan/Nup160^tm1Mdan Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6	MGI:6719494
cn33	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/? Trp53^tm5Tyj/Trp53^tm5Tyj	involves: 129S4/SvJae * C57BL/6	MGI:3700133
cn34	Crls1^tm1Geno/Crls1^tm1Geno Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6	MGI:6720819
cn35	Setd4^tm1c(KOMP)Wtsi/Setd4^tm1c(KOMP)Wtsi Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6 * C57BL/6N	MGI:6695300
cn36	Riok2^tm1c(KOMP)Wtsi/Riok2^+ Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6 * C57BL/6N	MGI:6712678
cn37	Atic^tm1c(EUCOMM)Hmgu/Atic^tm1c(EUCOMM)Hmgu Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7511822
cn38	Arih1^em3Gpt/Arih1^em3Gpt Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6JGpt	MGI:7410890
cn39	Xpo7^tm1c(KOMP)Wtsi/Xpo7^tm1c(KOMP)Wtsi Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6N	MGI:7388423
cn40	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/0 Smc5^tm1c(KOMP)Wtsi/Smc5^tm1d(KOMP)Wtsi	involves: 129S4/SvJae * C57BL/6N * CBA	MGI:5902337
cn41	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Tg(CAG-ANGPT1*)5Yo/0	involves: 129S4/SvJae * C57BL/6NCrlj * CBA/JNCrlj	MGI:5585468
cn42	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Rdh10^tm1c(KOMP)Wtsi/Rdh10^tm1d(KOMP)Wtsi	involves: 129S4/SvJae * C57BL/6N * FVB/NJ	MGI:7382902
cn43	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Rdh10^tm1c(KOMP)Wtsi/Rdh10^tm1c(KOMP)Wtsi	involves: 129S4/SvJae * C57BL/6N * FVB/NJ	MGI:7382903
cn44	Wbp1l^tm2c(EUCOMM)Hmgu/Wbp1l^tm2c(EUCOMM)Hmgu Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6N * SJL	MGI:6458733
cn45	Rest^tm1.1Bban/Rest^+ Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJaeSor * C57BL/6J	MGI:6378690
cn46	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Sprtn^tm1.1Yjm/Sprtn^tm1.1Yjm	involves: 129S/SvEv * 129S4/SvJae	MGI:6515755
cn47	Rad50^tm1Jpt/Rad50^tm3Jpt Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129/Sv * C57BL/6	MGI:5614076
cn48	Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+ Rad50^tm3Jpt/Rad50^tm4.1Jpt	involves: 129/Sv * C57BL/6	MGI:5614075
cn49	Vps33b^tm1.1Arte/Vps33b^tm1.1Arte Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: C57BL/6 * C57BL/6J	MGI:5770121
cn50	Vipas39^tm1c(KOMP)Mbp/Vipas39^tm1c(KOMP)Mbp Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: C57BL/6 * C57BL/6J * C57BL/6N	MGI:5817425

Genotype
MGI:5588435

cn1

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor^{tm1(Grem1)Svok}
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae

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

limbs/digits/tail

abnormal digit morphology ( J:214075 )

• following tamoxifen administration at E9.5, hindlimb digits exhibit nubs (ectopic pieces of cartilage (7/12)

• following tamoxifen administration at E10.5, hindlimb digits exhibit nubs (5/5

• following tamoxifen administration at E9.5 and E10.5, all forelimb digits exhibit nubs

• following tamoxifen administration at E11.5, some forelimb digits exhibit nubs (3/5)

• following tamoxifen administraion, hindlimbs and forelimbs do not form nubs or polydactyly after E11.5

polydactyly ( J:214075 )

• following tamoxifen administration at E9.5, hindlimb digits exhibit polydactyly (5/12)

• following tamoxifen administration, hindlimbs and forelimbs do not form nubs or polydactyly after E11.5

Genotype
MGI:5447473

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor^tm1(Pyy)Paba
• Genetic Background: involves: 129S4/SvJae

Lower bone mass and reduced bone size in Gt(ROSA)26Sor^tm1(Pyy)Paba/Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj} females

growth/size/body

decreased lean body mass ( J:189512 )

♀ • in females prior to tamoxifen treatment

skeleton

short femur ( J:189512 )

♀ • in females after tamoxifen treatment

small vertebrae ( J:189512 )

♀ • decrease in vertebral height in females after tamoxifen treatment

abnormal bone structure ( J:189512 )

abnormal osteoclast morphology ( J:189512 )

• increase in osteoclast surface in the femoral metaphysis in tamoxifen treated males and females

increased osteoclast cell number ( J:189512 )

♀ • in tamoxifen treated females

decreased bone mineral density of femur ( J:189512 )

♀ • decreased bone mineral density in the femur of females after tamoxifen treatment

decreased trabecular bone volume ( J:189512 )

♀ • in the distal femora and lumbar vertebrae in tamoxifen treated females

decreased compact bone area ( J:189512 )

♀ • in tamoxifen treated females

abnormal bone mineralization ( J:189512 )

• decrease in the mineral apposition rate in the distal femoral metaphysis of tamoxifen treated males and females

• cancellous bone formation rate and mid-femoral endocortical MAR are decreased in tamoxifen treated females

decreased bone strength ( J:189512 )

♀ • reduced mean polar moment of inertia in tamoxifen treated females

hematopoietic system

abnormal osteoclast morphology ( J:189512 )

• increase in osteoclast surface in the femoral metaphysis in tamoxifen treated males and females

increased osteoclast cell number ( J:189512 )

♀ • in tamoxifen treated females

immune system

abnormal osteoclast morphology ( J:189512 )

• increase in osteoclast surface in the femoral metaphysis in tamoxifen treated males and females

increased osteoclast cell number ( J:189512 )

♀ • in tamoxifen treated females

limbs/digits/tail

short femur ( J:189512 )

♀ • in females after tamoxifen treatment

Genotype
MGI:6323622

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Secisbp2^tm1.1Amdu/Secisbp2^tm1.2Amdu
• Genetic Background: B6(129S4)-Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj} Secisbp2^tm1.1Amdu Secisbp2^tm1.2Amdu

mortality/aging

premature death ( J:251875 )

• mice treated with tamoxifen starting at P25 show severe failure to thrive and lethality by 3 weeks after tamoxifen injection in most mice

• mice treated with tamoxifen for 4 days starting at P28 to P35 survive to at least 10 months after tamoxifen injection

growth/size/body

decreased body weight ( J:251875 )

• mice exhibit 16% decreased body weight 2 weeks after starting tamoxifen injection, and 24% and 26% decreased weight in males and females, respectively, at 4 weeks postinjection

endocrine/exocrine glands

abnormal pituitary gland physiology ( J:251875 )

• the product of serum TSH and T4 levels, known as T4 resistance index, is increased 5.3-fold in males and 12.4-fold in females after tamoxifen treatment, indicating pituitary resistance to circulating TH levels

homeostasis/metabolism

increased circulating thyroid-stimulating hormone level ( J:251875 )

• males exhibit a 3.5-fold increase and females a 9.8-fold increase in TSH 4 weeks after starting tamoxifen injection

abnormal thyroid hormone level ( J:251875 )

• males exhibit a 2.3-fold increase and females a 1.4-fold increase in rT3 levels 4 weeks after starting tamoxifen injection

• however, T3 levels are similar to controls

increased thyroxine level ( J:251875 )

• males exhibit a 1.5-fold increase and females a 1.3-fold increase in T4 levels 4 weeks after starting tamoxifen injection

• liver T4 content is increased by 1.4-fold in both tamoxifen treated males and females

• however, liver T3 content is normal

decreased triiodothyronine level ( J:251875 )

• tamoxifen treated mice exhibit a 0.7-fold decrease in T3/T4 ratio, indicating decreased efficiency in generating circulating T3

• cerebral T3 content is decreased 29% and 35% in males and females, respectively, after tamoxifen treatment

• the ratio of liver to serum T3 concentrations is decreased and ratios of T3/T4 content is decreased by 0.6- and 0.7-fold in tamoxifen-treated males and females, respectively, suggesting a decrease of local T3 generation

• however, serum T3 levels and liver T3 content are normal in tamoxifen-treated mice

abnormal enzyme/coenzyme activity ( J:251875 )

• type 1 deiodinase (D1) enzymatic activity is decreased by 69% and 51% in males and females, respectively

• type 2 deiodinase (D2) enzymatic activity is decreased by 47% and 52% in males and females, respectively, after tamoxifen treatment

nervous system

abnormal pituitary gland physiology ( J:251875 )

• the product of serum TSH and T4 levels, known as T4 resistance index, is increased 5.3-fold in males and 12.4-fold in females after tamoxifen treatment, indicating pituitary resistance to circulating TH levels

reproductive system

infertility ( J:251875 )

• mice treated with tamoxifen starting at P28 are infertile in matings with control mice for more than 6 months

Genotype
MGI:5614488

cn4

• Allelic Composition: Gnai2^tm2.1Rneu/Gnai2^tm2.1Rneu; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm1(cre/ert2)Tyj} Gnai2^tm2.1Rneu

cardiovascular system

abnormal response to cardiac infarction ( J:217517 )

• postischemic recovery of +dP/dT and -dP/dT is enhanced in hearts from tamoxifen treated animals as compared to controls

• postischemic recovery of developed pressure is enhanced in hearts from tamoxifen treated animals as compared to controls

decreased myocardial infarct size ( J:217517 )

• following tamoxifen administration, ischemia-induced myocardial infarct size is decreased as compared to controls

homeostasis/metabolism

abnormal response to cardiac infarction ( J:217517 )

• postischemic recovery of +dP/dT and -dP/dT is enhanced in hearts from tamoxifen treated animals as compared to controls

• postischemic recovery of developed pressure is enhanced in hearts from tamoxifen treated animals as compared to controls

decreased myocardial infarct size ( J:217517 )

• following tamoxifen administration, ischemia-induced myocardial infarct size is decreased as compared to controls

Genotype
MGI:5467841

cn5

• Allelic Composition: Mirc14^tm1.1Czc/Mirc14^tm1.1Czc; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: either: (involves: 129P2/OlaHsd * 129S4/SvJae * 129S4/SvJaeSor) or (involves: 129P2/OlaHsd * 129S4/SvJae * 129S4/SvJaeSor * C57BL/6)

immune system

thymus hypoplasia ( J:188125 )

• in tamoxifen-treated mice

decreased double-positive T cell number ( J:188125 )

• in tamoxifen-treated mice

hematopoietic system

thymus hypoplasia ( J:188125 )

• in tamoxifen-treated mice

decreased double-positive T cell number ( J:188125 )

• in tamoxifen-treated mice

endocrine/exocrine glands

thymus hypoplasia ( J:188125 )

• in tamoxifen-treated mice

Genotype
MGI:6106902

cn6

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}; Nus1^tm1.1Qrm/Nus1^tm1.1Qrm
• Genetic Background: involves: 129 * C57BL/6 * SJL

homeostasis/metabolism

abnormal lipid homeostasis ( J:243753 )

♀ • induction of hepatic lipogenesis when fed Western diet

increased liver free fatty acids level ( J:243753 )

♀ • when fed Western diet

increased liver triglyceride level ( J:243753 )

♀ • when fed Western diet

liver/biliary system

increased liver free fatty acids level ( J:243753 )

♀ • when fed Western diet

increased liver triglyceride level ( J:243753 )

♀ • when fed Western diet

hepatic steatosis ( J:243753 )

♀ • when fed Western diet

Genotype
MGI:5763151

cn7

• Allelic Composition: Smg6^tm1.1Zqw/Smg6^tm1.1Zqw; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

cellular

cellular phenotype ( J:222980 )

N • tamoxifen-treated embryonic stem cells exhibit normal viability and self-renewal

abnormal cell morphology ( J:222980 )

• tamoxifen-treated embryonic stem cells fail to differentiate in vitro and in vivo

abnormal telomere morphology ( J:222980 )

• tamoxifen-treated embryonic stem cells and embryonic fibroblasts exhibit defective telomere maintenance

abnormal cell physiology ( J:222980 )

• tamoxifen-treated embryonic stem cells exhibit nonsense-mediated mRNA decay

Genotype
MGI:5629844

cn8

• Allelic Composition: Hprt1^{tm6(CAG-fat-1)Geno}/Y; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

homeostasis/metabolism

abnormal fatty acids level ( J:213660 )

♂ • tamoxifen-treated mice exhibit enrichment in phospholipid total n-3 polyunsaturated fatty acid (predominantly docosahexaenoic acid) with lesser contributions to total relative n-3 polyunsaturated fatty acid enrichment from 22:5n-3 in the liver, kidney and muscle compared with control mice

♂ • tamoxifen-treated mice exhibit a reduction in n-6 polyunsaturated fatty acid species, 22:5n-6 and 22:4n-6 in the liver, kidney and a small overall decrease in total n-6 polyunsaturated fatty acid content in the kidney and liver compared with control mice

♂ • tamoxifen treated mice exhibit a small difference in n-6/n-3 polyunsaturated fatty acid ratio compared with control mice

♂ • however, mice exhibit normal total saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid

Genotype
MGI:6695306

cn9

• Allelic Composition: Trp53^tm1Brn/Trp53^tm1Brn; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

mortality/aging

increased mortality induced by gamma-irradiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation

neoplasm

decreased tumor latency ( J:297725 )

• gamma-irradiated, tamoxifen-treated adult mice show accelerated thymic lymphoma formation

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation

Genotype
MGI:6695307

cn10

• Allelic Composition: Trp53^tm1Brn/Trp53⁺; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

mortality/aging

increased mortality induced by gamma-irradiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice die between 100 and 200 days after irradiation

neoplasm

decreased tumor latency ( J:297725 )

• gamma-irradiated, tamoxifen-treated adult mice show accelerated thymic lymphoma formation

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice die between 100 and 200 days after irradiation

Genotype
MGI:5007795

cn11

• Allelic Composition: Kras^tm5Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

neoplasm

increased sarcoma incidence ( J:172206 )

• mice treated with flp-expressing adenovirus and tamoxifen on the same day exhibit sarcomas

• however, delayed tamoxifen-treatment reduces sarcoma formation

Genotype
MGI:5629845

cn12

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Hprt1^{tm6(CAG-fat-1)Geno}/Hprt1^{tm6(CAG-fat-1)Geno}
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

homeostasis/metabolism

abnormal fatty acids level ( J:213660 )

♀ • tamoxifen-treated mice exhibit enrichment in phospholipid total n-3 polyunsaturated fatty acid (predominantly docosahexaenoic acid) with lesser contributions to total relative n-3 polyunsaturated fatty acid enrichment from 22:5n-3 in the liver, kidney and muscle compared with control mice

♀ • tamoxifen-treated mice exhibit a reduction in n-6 polyunsaturated fatty acid species, 22:5n-6 and 22:4n-6 in the liver, kidney and a small overall decrease in total n-6 polyunsaturated fatty acid content in the kidney and liver compared with control mice

♀ • tamoxifen treated mice exhibit a small difference in n-6/n-3 polyunsaturated fatty acid ratio compared with control mice

♀ • however, mice exhibit normal total saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid

Genotype
MGI:6695305

cn13

• Allelic Composition: Setd4^{tm1c(KOMP)Wtsi}/Setd4^{tm1c(KOMP)Wtsi}; Trp53^tm1Brn/Trp53⁺; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6N
• Cell Lines: EPD0225_5_D10

neoplasm

neoplasm ( J:297725 )

N • sham-irradiated, tamoxifen-treated mice show no significant differences in spontaneous tumor development or survival relative to mice that are heterozygous for Trp53^tm1Brn and Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj} but wild-type for Setd4

abnormal tumor latency ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice fail to display a delay in the development of radiation-induced thymic lymphomas

Genotype
MGI:6695303

cn14

• Allelic Composition: Setd4^{tm1c(KOMP)Wtsi}/Setd4^{tm1c(KOMP)Wtsi}; Trp53^tm1Brn/Trp53^tm1Brn; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6N
• Cell Lines: EPD0225_5_D10

mortality/aging

increased mortality induced by gamma-irradiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation

neoplasm

decreased metastatic potential ( J:297725 )

• gamma-irradiated tamoxifen-treated mice die mainly of non-disseminated thymic lymphomas, unlike mice that are homozygous for Setd4^{tm1c(KOMP)Wtsi}and heterozygous for Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj} where tumors are widely disseminated to other organs

increased tumor growth/size ( J:297725 )

• in gamma-irradiated tamoxifen-treated mice, thymic lymphomas are significantly larger in size/weight relative to those in mice that are only homozygous for Setd4^{tm1c(KOMP)Wtsi}and heterozygous for Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}

abnormal tumor latency ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice fail to display a delay in the development of radiation-induced thymic lymphomas

decreased tumor latency ( J:297725 )

• sham-irradiated, tamoxifen-treated double mutant mice show accelerated spontaneous tumor development relative to mice that are only homozygous for Trp53^tm1Brn and heterozygous for Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation

Genotype
MGI:7511828

cn15

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Atic^{tm1c(EUCOMM)Hmgu}/Atic^{tm1c(EUCOMM)Hmgu}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * C57BL/6N

cardiovascular system

decreased susceptibility to atherosclerosis ( J:338121 )

• both sexes of tamoxifen-treated mice fed a Western diet for 12 weeks show a significant decrease in atherosclerotic lesion size in whole aortas as well as smaller lesion areas and less lipid deposition in the aortic sinuses than control mice

• ACTA2 staining of aortic sinuses showed a significant reduction in the vascular smooth muscle cell (VSMC) content of atherosclerotic lesions in both sexes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:338121 )

N • both male and female mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks show no significant differences in plasma glucose levels relative to controls

decreased circulating cholesterol level ( J:338121 )

♂ • male, but not female, mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks show a modest reduction in plasma cholesterol levels relative to controls

increased circulating triglyceride level ( J:338121 )

♀ • female, but not male, mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks exhibit a significant increase in plasma triglyceride levels relative to controls

Genotype
MGI:6362663

cn16

• Allelic Composition: Htatsf1^tm1Jakn/Htatsf1^tm1Jakn; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

embryo

abnormal pluripotent precursor cell morphology ( J:271373 )

• embryonic stem cells treated with tamoxifen exhibit reduced ability to re-form colonies compared with control cells

Genotype
MGI:5693400

cn17

• Allelic Composition: Bmi1^tm1Sgon/Bmi1^tm1Sgon; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/?
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

mortality/aging ( J:221849 )

N • tamoxifen induction of cre at 4 weeks of age

premature death ( J:221849 )

• mice die at 28-32 weeks of age

hematopoietic system

hematopoietic system phenotype ( J:221849 )

N • tamoxifen induction of cre at 4 weeks of age

N • normal myeloid cell numbers 4 months after cre induction

decreased lymphocyte cell number ( J:221849 )

• 4 months after cre induction

decreased hematopoietic stem cell number ( J:221849 )

• primitive hematopoietic stem cells is lower in bone marrow 4 months after cre induction

decreased spleen weight ( J:221849 )

• decreased spleen mass 4 months after cre induction

immune system

immune system phenotype ( J:221849 )

N • tamoxifen induction of cre at 4 weeks of age

decreased lymphocyte cell number ( J:221849 )

• 4 months after cre induction

decreased spleen weight ( J:221849 )

• decreased spleen mass 4 months after cre induction

Genotype
MGI:7327640

cn18

• Allelic Composition: Aldh1a1^tm1Gdu/Aldh1a1^tm1Gdu; Aldh1a2^tm1.1Mbp/Aldh1a2^tm1.1Mbp; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

reproductive system

abnormal spermatogenesis ( J:324715 )

♂ • block at the progression at the conversion of A spermatogonia to A1 following chronic treatment with tamoxifen

azoospermia ( J:324715 )

♂ • sperm depletion occurs after chronic administration of tamoxifen

male infertility ( J:324715 )

♂

cellular

azoospermia ( J:324715 )

♂ • sperm depletion occurs after chronic administration of tamoxifen

Genotype
MGI:5305074

cn19

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Tacc3^tm1.1Tno/Tacc3⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

neoplasm

increased T cell derived lymphoma incidence ( J:179414 )

• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in a rapid increase in tumor volume

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:179414 )

• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in a rapid increase in tumor volume

Genotype
MGI:5305073

cn20

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Tacc3^tm1.1Tno/Tacc3^tm1.2Tno; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

neoplasm

increased T cell derived lymphoma incidence ( J:179414 )

• in the absence of 4OHT, mutants develop thymic lymphoma tumors

decreased lymphoma incidence ( J:179414 )

• administration of 4-hydroxytamoxifen (4OHT) to induce Cre recombination results in regression of autochthonous thymic lymphoma, with a reduction in tumor volume to 96% and 26% of original volume, over 3 and 10 days, respectively

• regression of tumors is due to apoptosis in thymic lymphoma

• 4OHT treatment of mutants results in massive apoptosis in thymic lymphomas but not in normal thymic tissue or other tissues

• lymphoma cells contain multi-polar spindles, indicating aberrant spindle formation, resulting in mitotic arrest and rapid cell death

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:179414 )

• in the absence of 4OHT, mutants develop thymic lymphoma tumors

Genotype
MGI:5140103

cn21

• Allelic Composition: Trp53^tm3Att/Trp53^tm3Att; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/?
• Genetic Background: involves: 129S4/SvJae

cellular

cellular phenotype ( J:173395 )

N • apoptosis observed after tamoxifen treatment and measured 6 hours after gamma irradiation as is observed in controls

Genotype
MGI:3776023

cn22

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:132357 )

• adult mice develop widespread hyperplasia throughout the colonic epithelium

abnormal large intestine crypts of Lieberkuhn morphology ( J:132357 )

• hyperplasia is typified by lengthening of the crypts in adult mice

abnormal colon goblet cell morphology ( J:132357 )

• large, prominent goblet cells develop in the colon in adult mice

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:132357 )

• hyperplasia is typified by lengthening of the crypts in adult mice

abnormal colon goblet cell morphology ( J:132357 )

• large, prominent goblet cells develop in the colon in adult mice

cellular

abnormal colon goblet cell morphology ( J:132357 )

• large, prominent goblet cells develop in the colon in adult mice

Genotype
MGI:5140097

cn23

• Allelic Composition: Trp53^tm1Att/Trp53^tm1Att; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/?
• Genetic Background: involves: 129S4/SvJae

cellular

decreased apoptosis ( J:173395 )

• no apoptosis in mice treated with tamoxifen measured 6 hours after radiation treatment

Genotype
MGI:5585466

cn24

• Allelic Composition: Angpt1^tm1.1Yona/Angpt1^tm1.1Yona; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae

cardiovascular system

abnormal retina blood vessel morphology ( J:213456 )

• tamoxifen-treated mice exhibit decreased radial length, vascular density, endothelial cell proliferative activity, sprouting activity, and pericyte coverage compared with control mice

• tamoxifen-treated mice exhibit decreased vascular density in the superficial and deep vascular plexus layers compared with control mice

• tamoxifen-treated mice exhibit disorganized, regressed, disconnected and dilated retinal vessels compared with control mice

increased vascular permeability ( J:213456 )

• 4-fold increased vessel leakage following oxygen-induced retinopathy in tamoxifen-treated mice

vision/eye

abnormal retina blood vessel morphology ( J:213456 )

• tamoxifen-treated mice exhibit decreased radial length, vascular density, endothelial cell proliferative activity, sprouting activity, and pericyte coverage compared with control mice

• tamoxifen-treated mice exhibit decreased vascular density in the superficial and deep vascular plexus layers compared with control mice

• tamoxifen-treated mice exhibit disorganized, regressed, disconnected and dilated retinal vessels compared with control mice

increased susceptilbility to retina ischemic injury ( J:213456 )

• following oxygen-induced retinopathy, mice exhibit increased avascular area, neovascular tuft area and reduced pericyte coverage in the superficial layer with disorganized, regressed, disconnected and dilated deep layer vessels, 4-fold increased vessel leakage and 4-fold increase in multifocal hemorrhages compared with control mice

nervous system

decreased astrocyte number ( J:213456 )

• decrease in GFAP+ cell densities in tamoxifen-treated mice

• however, the number of Pax2+ astrocytes is normal

homeostasis/metabolism

increased susceptilbility to retina ischemic injury ( J:213456 )

• following oxygen-induced retinopathy, mice exhibit increased avascular area, neovascular tuft area and reduced pericyte coverage in the superficial layer with disorganized, regressed, disconnected and dilated deep layer vessels, 4-fold increased vessel leakage and 4-fold increase in multifocal hemorrhages compared with control mice

Genotype
MGI:5140099

cn25

• Allelic Composition: Trp53^tm4Att/Trp53^tm4Att; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/?
• Genetic Background: involves: 129S4/SvJae

cellular

decreased apoptosis ( J:173395 )

• no apoptosis in mice treated with tamoxifen when measured 6 hours after radiation treatment

Genotype
MGI:5904345

cn26

• Allelic Composition: E2f4^tm2.1Lees/E2f4^tm2.1Lees; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6

respiratory system

abnormal respiratory motile cilium morphology ( J:241925 )

• mice treated with 4-hydroxytamoxifen show disruption of multiciliogenesis in lung epithelium

• 4-hydroxytamoxifen treated mice are unable to form deuterosomes and Pcm1-containing aggregates in lung epithelium

• however, primary cilia formation occurs

cellular

abnormal respiratory motile cilium morphology ( J:241925 )

• mice treated with 4-hydroxytamoxifen show disruption of multiciliogenesis in lung epithelium

• 4-hydroxytamoxifen treated mice are unable to form deuterosomes and Pcm1-containing aggregates in lung epithelium

• however, primary cilia formation occurs

Genotype
MGI:6867021

cn27

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Supt5^tm1.1Rrp/Supt5^tm1.2Rrp
• Genetic Background: involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6

cellular

abnormal fibroblast physiology ( J:319843 )

• decreased viability in tamoxifen-treated mouse embryonic stem cells after 96 h

• however, cells exhibit no global elongation defects or decreased elongation rates

Genotype
MGI:5494478

cn28

• Allelic Composition: Agr2^tm1Lex/Agr2^tm1Lex; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * 129S5/SvEvBrd * C57BL/6

cellular

increased cell proliferation ( J:195573 )

• 1.5- and 3.3-fold in the corpus and antrum, respectively, of tamoxifen treated mice at 8 weeks

Genotype
MGI:5544446

cn29

• Allelic Composition: Pde6b^atrd1/Pde6b^tm1Eye; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * BALB/cAnN * C3H/HeN * C57BL/6J

vision/eye

vision/eye phenotype ( J:200898 )

N • treatment with tamoxifen at E0.5 or E12 prevents the progressive photoreceptor degeneration seen in heterozygous mice without cre expression

N • treatment with tamoxifen at E0.5 also rescues the hyper-autofluorescence fundus phenotype

abnormal ocular fundus morphology ( J:200898 )

• following tamoxifen treatment at E12 or P1and P2, at 18 weeks of age hyper-autofluorescence spots of heterogeneous size and non-uniform distribution are seen on the fundus

• tamoxifen treatment at P1 fails to rescue the fundus hyper-autofluorescence phenotype

abnormal retina blood vessel morphology ( J:200898 )

• tamoxifen treatment at E12 or P1 and P2 results in partial rescue of progressive arteriolar narrowing at 18 weeks of age

• tamoxifen treatment at E0.5 results in complete rescue of arteriolar narrowing at 18 weeks of age

• tamoxifen treatment at P1 fails to rescue arteriolar narrowing

decreased retina photoreceptor cell number ( J:200898 )

• only treatment with tamoxifen at E0.5 resulted in photoreceptor numbers similar to controls after P18

• mice treated with tamoxifen at E12 or P1 have fewer photoreceptors by 18 weeks of age compared to controls

abnormal retina cone cell morphology ( J:200898 )

• cones show a distinct trailing edge/ring-shaped shape, reminiscent of a flame instead of the normal small, round, punctate shape at E12

retina photoreceptor degeneration ( J:200898 )

• treatment with a single dose of tamoxifen at P1 fails to prevent progressive retinal photoreceptor degeneration

• treatment with 2 doses of tamoxifen at P1 and P2 partially rescues the progressive retinal photoreceptor degeneration

nervous system

decreased retina photoreceptor cell number ( J:200898 )

• only treatment with tamoxifen at E0.5 resulted in photoreceptor numbers similar to controls after P18

• mice treated with tamoxifen at E12 or P1 have fewer photoreceptors by 18 weeks of age compared to controls

abnormal retina cone cell morphology ( J:200898 )

• cones show a distinct trailing edge/ring-shaped shape, reminiscent of a flame instead of the normal small, round, punctate shape at E12

retina photoreceptor degeneration ( J:200898 )

• treatment with a single dose of tamoxifen at P1 fails to prevent progressive retinal photoreceptor degeneration

• treatment with 2 doses of tamoxifen at P1 and P2 partially rescues the progressive retinal photoreceptor degeneration

cardiovascular system

abnormal retina blood vessel morphology ( J:200898 )

• tamoxifen treatment at E12 or P1 and P2 results in partial rescue of progressive arteriolar narrowing at 18 weeks of age

• tamoxifen treatment at E0.5 results in complete rescue of arteriolar narrowing at 18 weeks of age

• tamoxifen treatment at P1 fails to rescue arteriolar narrowing

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa 40		DOID:0110375	OMIM:613801	J:200898

Genotype
MGI:5897612

cn30

• Allelic Composition: Ddrgk1^{tm1c(EUCOMM)Hmgu}/Ddrgk1^{tm1c(EUCOMM)Hmgu}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6N
• Cell Lines: HEPD0618_2_D02

mortality/aging

premature death ( J:231701 )

• 3 weeks after tamoxifen treatment

hematopoietic system

abnormal embryonic erythropoiesis ( J:231701 )

• tamoxifen-treated mice exhibit impaired erythroid development at multiple stages

decreased erythrocyte cell number ( J:231701 )

• after tamoxifen treatment

decreased hemoglobin content ( J:231701 )

• after tamoxifen treatment

decreased granulocyte number ( J:231701 )

• after tamoxifen treatment

decreased lymphocyte cell number ( J:231701 )

• after tamoxifen treatment

decreased monocyte cell number ( J:231701 )

• after tamoxifen treatment

pancytopenia ( J:231701 )

• severe in adult mice treated with tamoxifen

abnormal hematopoietic stem cell physiology ( J:231701 )

• cell-autonomous impairment of hematopoietic stem cell function with activation of unfolded protein response and cell death after tamoxifen treatment

embryo

abnormal embryonic erythropoiesis ( J:231701 )

• tamoxifen-treated mice exhibit impaired erythroid development at multiple stages

growth/size/body

weight loss ( J:231701 )

• after tamoxifen treatment

immune system

decreased granulocyte number ( J:231701 )

• after tamoxifen treatment

decreased lymphocyte cell number ( J:231701 )

• after tamoxifen treatment

decreased monocyte cell number ( J:231701 )

• after tamoxifen treatment

Genotype
MGI:5825319

cn31

• Allelic Composition: Ufl1^{tm1c(EUCOMM)Wtsi}/Ufl1^{tm1c(EUCOMM)Wtsi}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6N

mortality/aging

premature death ( J:238253 )

• 3 weeks after tamoxifen treatment

hematopoietic system

anemia ( J:238253 )

• in tamoxifen-treated mice

decreased erythroid progenitor cell number ( J:238253 )

• in tamoxifen-treated mice

decreased erythrocyte cell number ( J:238253 )

• in tamoxifen-treated mice

decreased hematocrit ( J:238253 )

• in tamoxifen-treated mice

decreased hemoglobin content ( J:238253 )

• in tamoxifen-treated mice

thrombocytopenia ( J:238253 )

• in tamoxifen-treated mice

decreased leukocyte cell number ( J:238253 )

• in tamoxifen-treated mice

decreased granulocyte number ( J:238253 )

• in tamoxifen-treated mice

decreased lymphocyte cell number ( J:238253 )

• in tamoxifen-treated mice

decreased monocyte cell number ( J:238253 )

• in tamoxifen-treated mice

pancytopenia ( J:238253 )

• in tamoxifen-treated mice

abnormal bone marrow cell physiology ( J:238253 )

• tamoxifen-treated bone marrow cells exhibit increased ER stress and increased unfolded protein response compared with control cells

growth/size/body

weight loss ( J:238253 )

• in tamoxifen-treated mice

cellular

abnormal autophagy ( J:238253 )

• tamoxifen-treated mice exhibit decreased autophagic degradation with increased reactive oxygen species, mitochondrial mass, DNA damage, and enhanced cell death in hematopoietic cells unlike wild-type mice

immune system

decreased leukocyte cell number ( J:238253 )

• in tamoxifen-treated mice

decreased granulocyte number ( J:238253 )

• in tamoxifen-treated mice

decreased lymphocyte cell number ( J:238253 )

• in tamoxifen-treated mice

decreased monocyte cell number ( J:238253 )

• in tamoxifen-treated mice

homeostasis/metabolism

abnormal autophagy ( J:238253 )

• tamoxifen-treated mice exhibit decreased autophagic degradation with increased reactive oxygen species, mitochondrial mass, DNA damage, and enhanced cell death in hematopoietic cells unlike wild-type mice

Genotype
MGI:6719494

cn32

• Allelic Composition: Nup160^tm1Mdan/Nup160^tm1Mdan; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

hematopoietic system

abnormal hematopoietic stem cell physiology ( J:301567 )

• hematopoietic progenitors at 72 hours of tamoxifen treatment show a decrease in the number of EdU+ positive cells and an increase in the G1 population, indicating an arrest in G1

decreased hematopoietic stem cell proliferation ( J:301567 )

• primary hematopoietic progenitors in culture treated with tamoxifen show a decrease in cell numbers over time, however an increase in cell death is not seen, indicating a cell cycle arrest

cellular

decreased hematopoietic stem cell proliferation ( J:301567 )

• primary hematopoietic progenitors in culture treated with tamoxifen show a decrease in cell numbers over time, however an increase in cell death is not seen, indicating a cell cycle arrest

Genotype
MGI:3700133

cn33

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/?; Trp53^tm5Tyj/Trp53^tm5Tyj
• Genetic Background: involves: 129S4/SvJae * C57BL/6

neoplasm

tumor regression ( J:118233 )

• mice with radiation-induced tumors that are subsequently treated with tamoxifen show tumor regression (7 of 10) or cessation of tumor progression (2 of 10)

Genotype
MGI:6720819

cn34

• Allelic Composition: Crls1^tm1Geno/Crls1^tm1Geno; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

homeostasis/metabolism

decreased oxygen consumption ( J:266083 )

• primary brown adipocytes from tamoxifen-treated mice show a significant reduction in norepinephrine (NE)-induced uncoupled respiration relative to control cells

Genotype
MGI:6695300

cn35

• Allelic Composition: Setd4^{tm1c(KOMP)Wtsi}/Setd4^{tm1c(KOMP)Wtsi}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6N
• Cell Lines: EPD0225_5_D10

mortality/aging

decreased mortality induced by ionizing radiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice show delayed thymic lymphoma-mediated death and improved overall survival with a median survival of 245 days versus 195 days in oil-treated controls; 500 days after irradiation, the lymphoma-free survival 22% versus 9.4% in oil-treated controls

• however, non-irradiated tamoxifen-treated adults show no significant differences in survival up to 700 days relative to oil-treated controls

neoplasm

abnormal tumor pathology ( J:297725 )

• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice exhibit a lower % of cleaved caspase-3 positive cells in their lymphomas than oil-treated controls

• although radiation-induced T cell lymphomas are largely clonogenic, thymic lymphomas of tamoxifen-treated mice are composed mainly of CD4+ CD8+ double positive cells whereas tumors in oil-treated control mice are largely composed of CD8+ single positive cells

• radiation-induced thymic lymphomas of tamoxifen-treated mice exhibit more chromosomal inversions but fewer deletion events than control tumors

increased metastatic potential ( J:297725 )

• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice show a more widespread infiltration of peripheral organs (spleen, liver, kidney, and lung) by T-lymphoma cells and a higher tumor dissemination score at the time of death relative to oil-treated controls

decreased tumor growth/size ( J:297725 )

• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice that die within the first 195 days post-irradiation show a slight reduction in the size/weight of lymphomas relative to oil-treated controls

• however, no significant difference in primary thymus tumor weight is noted at the time of death

increased tumor latency ( J:297725 )

• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice show a significant delay in the development of radiation-induced thymic lymphomas and lymphoma-mediated death relative to oil-treated controls, likely due to slower tumor enlargement in the thymus

• however, non-irradiated tamoxifen-treated adults show no obvious growth retardation or tumor development up to 700 days relative to oil-treated controls

homeostasis/metabolism

decreased mortality induced by ionizing radiation ( J:297725 )

• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice show delayed thymic lymphoma-mediated death and improved overall survival with a median survival of 245 days versus 195 days in oil-treated controls; 500 days after irradiation, the lymphoma-free survival 22% versus 9.4% in oil-treated controls

• however, non-irradiated tamoxifen-treated adults show no significant differences in survival up to 700 days relative to oil-treated controls

cellular

decreased apoptosis ( J:297725 )

• after exposure to total body gamma-irradiation, tamoxifen-treated adult mice exhibit a lower percentage of cleaved caspase-3 positive cells in their lymphomas than oil-treated controls

Genotype
MGI:6712678

cn36

• Allelic Composition: Riok2^{tm1c(KOMP)Wtsi}/Riok2⁺; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6N

hematopoietic system

anemia ( J:305794 )

• tamoxifen-induced mice develop anemia

decreased erythrocyte cell number ( J:305794 )

• tamoxifen-induced mice exhibit reduced peripheral blood red blood cell numbers

decreased hematocrit ( J:305794 )

• tamoxifen-induced mice exhibit reduced hematocrit

decreased hemoglobin content ( J:305794 )

• tamoxifen-induced mice exhibit reduced hemoglobin

Genotype
MGI:7511822

cn37

• Allelic Composition: Atic^{tm1c(EUCOMM)Hmgu}/Atic^{tm1c(EUCOMM)Hmgu}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N

cardiovascular system

decreased vascular smooth muscle cell proliferation ( J:338121 )

• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo

abnormal vascular wound healing ( J:338121 )

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a dramatic reduction in the neointima area and neointima/medial area ratio in sections 200 to 1200 um from the site of ligation relative to control mice

• however, the external elastic lamina circumference of ligated common carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:338121 )

N • tamoxifen-treated mice fed a high-fat diet (HFD) for 12 weeks show no significant differences in HFD-induced body weight gain, fat content, leanness of body mass or fasting blood glucose levels relative to control mice, with no improvement in glucose clearance and insulin sensitivity

abnormal vascular wound healing ( J:338121 )

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a dramatic reduction in the neointima area and neointima/medial area ratio in sections 200 to 1200 um from the site of ligation relative to control mice

• however, the external elastic lamina circumference of ligated common carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected

cellular

decreased vascular smooth muscle cell proliferation ( J:338121 )

• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo

abnormal cell cycle ( J:338121 )

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

muscle

decreased vascular smooth muscle cell proliferation ( J:338121 )

• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo

Genotype
MGI:7410890

cn38

• Allelic Composition: Arih1^em3Gpt/Arih1^em3Gpt; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6JGpt

mortality/aging

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:330879 )

• in tamoxifen-treated mice

immune system

decreased interferon-beta secretion ( J:330879 )

• in tamoxifen-treated murine lung fibroblasts infected with HSV-1

decreased interleukin-6 secretion ( J:330879 )

• in tamoxifen-treated murine lung fibroblasts infected with HSV-1

increased susceptibility to Herpesvirales infection ( J:330879 )

• tamoxifen-treated murine lung fibroblasts infected with HSV-1 produce less IFN-beta and IL6

• HSV-1-infected, tamoxifen-treated mice exhibit increased viral titer in the spleen or brain and increased mortality compared with control mice

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:330879 )

• in tamoxifen-treated mice

Genotype
MGI:7388423

cn39

• Allelic Composition: Xpo7^{tm1c(KOMP)Wtsi}/Xpo7^{tm1c(KOMP)Wtsi}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6N

hematopoietic system

decreased hematocrit ( J:331429 )

• in tamoxifen-treated mice

Genotype
MGI:5902337

cn40

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/0; Smc5^{tm1c(KOMP)Wtsi}/Smc5^{tm1d(KOMP)Wtsi}
• Genetic Background: involves: 129S4/SvJae * C57BL/6N * CBA
• Cell Lines: EPD0395_1_F05

cellular

cellular phenotype ( J:240155 )

N • in embryonic stem cells after after 5 and 8 days of tamoxifen exposure

abnormal cell cycle ( J:240155 )

• 10% decrease in number of cells in S phase

• 10% increase in number of cells in G2 phase

abnormal mitosis ( J:240155 )

• mitotic delay

• accumulation of cells in G2 phase

• decreased condensin accumulation at pericentromeric regions in prometaphase cells

• increased condensin signal along chromosome arms in prometaphase cells

• increase in number of polyploid cells

• formation of chromosomal bridges

• lagging chromosomes

• reduced Plk1 enrichment at pericentromeric regions

• persistent localization of Aurkb along chromosome arms

abnormal mitotic spindle assembly checkpoint ( J:240155 )

• reduced Mad2l1 enrichment at pericentromeric regions

abnormal mitotic spindle morphology ( J:240155 )

increased mitotic index ( J:240155 )

• 10% increase in number of cells in G2 phase

mitotic nondisjunction ( J:240155 )

• 80% of cells could not complete accurate chromosome segregation

increased cell death ( J:240155 )

• acetylation at Lys379 of genotoxic stress marker Trp53, indicating stimulation of transcriptional activity

• cleavage of Parp1, indicating an apoptotic signal

abnormal cell differentiation ( J:240155 )

• shift in the pluripotent state by induction of differentiation marker expression

Genotype
MGI:5585468

cn41

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Tg(CAG-ANGPT1*)5Yo/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6NCrlj * CBA/JNCrlj

cardiovascular system

abnormal retina blood vessel morphology ( J:213456 )

• tamoxifen-treated mice exhibit increased radial length (1.5-fold), vascular density (1.6-fold), vessel diameter (1.9-fold), endothelial cell proliferative activity (2.0-fold) and sprouting activity (1.8-fold) compared with control mice

decreased vascular permeability ( J:213456 )

• 2.4-fold decreased vessel leakage following oxygen-induced retinopathy in tamoxifen-treated mice

vision/eye

abnormal retina blood vessel morphology ( J:213456 )

• tamoxifen-treated mice exhibit increased radial length (1.5-fold), vascular density (1.6-fold), vessel diameter (1.9-fold), endothelial cell proliferative activity (2.0-fold) and sprouting activity (1.8-fold) compared with control mice

decreased susceptilbility to retina ischemic injury ( J:213456 )

• following oxygen-induced retinopathy, mice exhibit decreased avascular area, neovascular tuft area and increased pericyte coverage in the superficial layer with more densely networked vessels in the central and middle regions of the deep layer, 2.4-fold decreased vessel leakage and 8.6-fold decrease in multifocal hemorrhages compared with control mice

nervous system

increased astrocyte number ( J:213456 )

• 1.3-fold increase in GFAP+ cell densities in tamoxifen-treated mice

• however, the number of Pax2+ astrocytes is normal

homeostasis/metabolism

decreased susceptilbility to retina ischemic injury ( J:213456 )

• following oxygen-induced retinopathy, mice exhibit decreased avascular area, neovascular tuft area and increased pericyte coverage in the superficial layer with more densely networked vessels in the central and middle regions of the deep layer, 2.4-fold decreased vessel leakage and 8.6-fold decrease in multifocal hemorrhages compared with control mice

Genotype
MGI:7382902

cn42

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Rdh10^{tm1c(KOMP)Wtsi}/Rdh10^{tm1d(KOMP)Wtsi}
• Genetic Background: involves: 129S4/SvJae * C57BL/6N * FVB/NJ

craniofacial

craniofacial phenotype ( J:278485 )

N • following tamoxifen treatment at E8.5 at E16.5 mandible size is not significantly different from controls, indicating this does not contribute to cleft palate

abnormal hyoid bone morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen

• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage and the hyoid primordium has a gentle M shape

decreased palatine bone horizontal plate size ( J:278485 )

• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5

palatal shelves fail to meet at midline ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 in 40% of embryos the palatal shelves have elevated but fail to grow to the midline

• however, in maxillary explant cultures shelves elevate and make medial contact at a similar rate to controls

cleft secondary palate ( J:278485 )

• at E16.5 in 36% of embryos following tamoxifen treatment at E8.5

abnormal palatal shelf elevation ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 only 33% of mutant embryos have both shelves elevated compared to 82% of controls

• following tamoxifen treatment at E8.5 at E14.5 palatal shelves appear to be obstructed by the arched tongue at the posterior end of the shelves

abnormal tongue muscle morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium

abnormal tongue position ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 the tongue is arched to the posterior rather than relatively flat as in controls

decreased tongue size ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 tongue volume is slightly reduced compared to controls

• however, no defects in intrinsic muscle morphology are seen

skeleton

abnormal hyoid bone morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen

• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage and the hyoid primordium has a gentle M shape

decreased palatine bone horizontal plate size ( J:278485 )

• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5

abnormal cricoid cartilage morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen

abnormal thyroid cartilage morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen

• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage

nervous system

abnormal motor neuron morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E11.5 the C1 motor nerve fuses directly to the CN XII nerve in 50% of embryos but never seen in controls

abnormal hypoglossal nerve morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E11.5 the C1 motor nerve fuses directly to the CN XII nerve in 50% of embryos but never seen in controls

respiratory system

abnormal cricoid cartilage morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen

abnormal thyroid cartilage morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 variable morphological defects are seen

• in some cases the hyoid primordium is ectopically fused to the laryngeal prominence of the thyroid cartilage

muscle

abnormal tongue muscle morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium

digestive/alimentary system

decreased palatine bone horizontal plate size ( J:278485 )

• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5

palatal shelves fail to meet at midline ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 in 40% of embryos the palatal shelves have elevated but fail to grow to the midline

• however, in maxillary explant cultures shelves elevate and make medial contact at a similar rate to controls

cleft secondary palate ( J:278485 )

• at E16.5 in 36% of embryos following tamoxifen treatment at E8.5

abnormal palatal shelf elevation ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 only 33% of mutant embryos have both shelves elevated compared to 82% of controls

• following tamoxifen treatment at E8.5 at E14.5 palatal shelves appear to be obstructed by the arched tongue at the posterior end of the shelves

abnormal tongue muscle morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium

abnormal tongue position ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 the tongue is arched to the posterior rather than relatively flat as in controls

decreased tongue size ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 tongue volume is slightly reduced compared to controls

• however, no defects in intrinsic muscle morphology are seen

growth/size/body

decreased palatine bone horizontal plate size ( J:278485 )

• feathery medial growth is lacking and ossified palatine bones do not approach the midline in 50% of embryos at E16.5 following tamoxifen treatment at E8.5

palatal shelves fail to meet at midline ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 in 40% of embryos the palatal shelves have elevated but fail to grow to the midline

• however, in maxillary explant cultures shelves elevate and make medial contact at a similar rate to controls

cleft secondary palate ( J:278485 )

• at E16.5 in 36% of embryos following tamoxifen treatment at E8.5

abnormal palatal shelf elevation ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 only 33% of mutant embryos have both shelves elevated compared to 82% of controls

• following tamoxifen treatment at E8.5 at E14.5 palatal shelves appear to be obstructed by the arched tongue at the posterior end of the shelves

abnormal tongue muscle morphology ( J:278485 )

• following tamoxifen treatment at E8.5 at E16.5 tongue muscles lack apparent attachment to the hyoid primordium

abnormal tongue position ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 the tongue is arched to the posterior rather than relatively flat as in controls

decreased tongue size ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5 tongue volume is slightly reduced compared to controls

• however, no defects in intrinsic muscle morphology are seen

Genotype
MGI:7382903

cn43

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Rdh10^{tm1c(KOMP)Wtsi}/Rdh10^{tm1c(KOMP)Wtsi}
• Genetic Background: involves: 129S4/SvJae * C57BL/6N * FVB/NJ

behavior/neurological

abnormal spontaneous fetal mouth movement ( J:278485 )

• following tamoxifen treatment at E8.5 at E14.5, head movements are not accompanied by detectable mouth opening or tongue movement unlike in controls

Genotype
MGI:6458733

cn44

• Allelic Composition: Wbp1l^{tm2c(EUCOMM)Hmgu}/Wbp1l^{tm2c(EUCOMM)Hmgu}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6N * SJL

hematopoietic system

abnormal bone marrow cell physiology ( J:284781 )

• tamoxifen-treated KIT+ bone marrow cells exhibit increased migration in a transwell assay in vitro and increased bone marrow homing in vivo

Genotype
MGI:6378690

cn45

• Allelic Composition: Rest^tm1.1Bban/Rest⁺; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6J

hearing/vestibular/ear

cochlear hair cell degeneration ( J:265659 )

• tamoxifen-injected mice show partial loss of hair cells

• organ of Corti cultures from P5 mice incubated with tamoxifen and treated with the HDAC inhibitors FK228 or SAHA show prevention of the tamoxifen-dependent degeneration of inner hair cells and outer hair cells

• treatment of P7-P9 tamoxifen-injected mice with SAHA fromP7 to P15 reduces the extent of tamoxifen-dependent hair cell loss in cochleas

increased or absent threshold for auditory brainstem response ( J:265659 )

• in P70-P80 mice treated with tamoxifen from P40 to P47

impaired hearing ( J:265659 )

• mice treated with tamoxifen from P40 to P47 show hearing loss one month after treatment

• mice treated with tamoxifen from P7 to P9 show hearing loss at P16

• treatment of P7-P9 tamoxifen-injected mice with SAHA from P7 to P15 reduces the tamoxifen-dependent shift in hearing threshold at low sound frequencies

nervous system

cochlear hair cell degeneration ( J:265659 )

• tamoxifen-injected mice show partial loss of hair cells

• organ of Corti cultures from P5 mice incubated with tamoxifen and treated with the HDAC inhibitors FK228 or SAHA show prevention of the tamoxifen-dependent degeneration of inner hair cells and outer hair cells

• treatment of P7-P9 tamoxifen-injected mice with SAHA fromP7 to P15 reduces the extent of tamoxifen-dependent hair cell loss in cochleas

Genotype
MGI:6515755

cn46

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Sprtn^tm1.1Yjm/Sprtn^tm1.1Yjm
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae

cellular

chromosomal instability ( J:297179 )

• failure to repair DNA-protein crosslinks (DPCs) in mouse embryo fibroblasts (MEFs)

• increased accumulation of camptothecin (CPT)-induced topoisomerase 1 cleavage complex (Top1cc) foci in MEFs

Genotype
MGI:5614076

cn47

• Allelic Composition: Rad50^tm1Jpt/Rad50^tm3Jpt; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:209141 )

• tamoxifen treated mice do not live beyond 2 weeks of age due to intestinal failure

digestive/alimentary system

abnormal intestine morphology ( J:209141 )

• intestinal defects are seen by day 9 of tamoxifen treatment

• die of intestinal failure

Genotype
MGI:5614075

cn48

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺; Rad50^tm3Jpt/Rad50^tm4.1Jpt
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:209141 )

• tamoxifen treated mice do not live beyond 2 weeks of age due to intestinal failure

digestive/alimentary system

abnormal intestine morphology ( J:209141 )

• intestinal defects are seen by day 9 of tamoxifen treatment

• die of intestinal failure

Genotype
MGI:5770121

cn49

• Allelic Composition: Vps33b^tm1.1Arte/Vps33b^tm1.1Arte; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J

Abnormal collagen structure in Vipas39^{tm1c(KOMP)Mbp}/Vipas39^{tm1c(KOMP)Mbp} Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺, and Vps33b^tm1.1Arte/Vps33b^tm1.1Arte Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺ mouse tail tendon

hematopoietic system

enlarged spleen ( J:222766 )

• in tamoxifen-treated mice

extramedullary hematopoiesis ( J:222766 )

• in the spleen of tamoxifen-treated mice

abnormal megakaryocyte morphology ( J:222766 )

• most bone marrow megakaryocytes in tamoxifen-treated mice lack immature granules and alpha granules

• some small alpha-granule-like structures are present in megakaryocytes of tamoxifen-treated mice

• megakaryocytes in tamoxifen-treated mice contain a large number of lamellar structures located close to the nucleus or to the periphery of the cells

• however, some megakaryocytes contain normal numbers of alpha granules

increased megakaryocyte cell number ( J:222766 )

• in the splenic red pulp and bone marrow of tamoxifen-treated mice

increased neutrophil cell number ( J:222766 )

• in tamoxifen-treated mice

decreased platelet alpha-granule number ( J:222766 )

• however, a subpopulation of platelets have normal alpha-granules

• lacking in most platelets of tamoxifen-treated mice

thrombocytosis ( J:222766 )

• without a change in platelet half-life in tamoxifen-treated mice

decreased mean platelet volume ( J:222766 )

• in tamoxifen-treated mice

decreased dendritic cell number ( J:222766 )

• in the spleen of tamoxifen-treated mice

decreased lymphocyte cell number ( J:222766 )

• in tamoxifen-treated mice

increased macrophage cell number ( J:222766 )

• in the spleen of tamoxifen-treated mice

increased monocyte cell number ( J:222766 )

• in tamoxifen-treated mice

decreased platelet aggregation ( J:222766 )

• in tamoxifen-treated mice

growth/size/body

growth/size/body region phenotype ( J:236095 )

N • no visceral abnormalities are observed after tamoxifen treatment

enlarged spleen ( J:222766 )

• in tamoxifen-treated mice

integument

alopecia ( J:236095 )

• mice develop hair loss 4 weeks after tamoxifen treatment

dry skin ( J:222766 , J:236095 )

• 5 weeks after tamoxifen treatment (J:222766)

• mice develop dry skin 4 weeks after tamoxifen treatment (J:236095)

scaly skin ( J:222766 , J:236095 )

• mild to severe 5 weeks after tamoxifen treatment (J:222766)

• mice develop scaly skin 4 weeks after tamoxifen treatment (J:236095)

skin lesions ( J:222766 )

• occasional macerated skin lesions 5 weeks after tamoxifen treatment

muscle

abnormal tendon collagen fibril morphology ( J:236095 )

• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed

• AFM showed a greater level of distortion with a far more irregular profile and height variation than in mice homozygous for Vipas39^{tm1c(KOMP)Mbp} and heterozygous for Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}

• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure

homeostasis/metabolism

decreased platelet aggregation ( J:222766 )

• in tamoxifen-treated mice

increased bleeding time ( J:222766 )

• in 9 of 15 tamoxifen-treated mice

• however, there is no sign of spontaneous bleeding

skeleton

abnormal tendon collagen fibril morphology ( J:236095 )

• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed

• AFM showed a greater level of distortion with a far more irregular profile and height variation than in mice homozygous for Vipas39^{tm1c(KOMP)Mbp} and heterozygous for Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}

• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure

immune system

enlarged spleen ( J:222766 )

• in tamoxifen-treated mice

increased neutrophil cell number ( J:222766 )

• in tamoxifen-treated mice

decreased dendritic cell number ( J:222766 )

• in the spleen of tamoxifen-treated mice

decreased lymphocyte cell number ( J:222766 )

• in tamoxifen-treated mice

increased macrophage cell number ( J:222766 )

• in the spleen of tamoxifen-treated mice

increased monocyte cell number ( J:222766 )

• in tamoxifen-treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ARC syndrome		DOID:0050763	OMIM:PS208085	J:222766

Genotype
MGI:5817425

cn50

• Allelic Composition: Vipas39^{tm1c(KOMP)Mbp}/Vipas39^{tm1c(KOMP)Mbp}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N

Abnormal collagen structure in Vipas39^{tm1c(KOMP)Mbp}/Vipas39^{tm1c(KOMP)Mbp} Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺, and Vps33b^tm1.1Arte/Vps33b^tm1.1Arte Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺ mouse tail tendon

integument

alopecia ( J:236095 )

• mice develop hair loss 4 weeks after tamoxifen treatment

dry skin ( J:236095 )

• mice develop dry skin 4 weeks after tamoxifen treatment

scaly skin ( J:236095 )

• mice develop scaly skin 4 weeks after tamoxifen treatment

muscle

abnormal tendon collagen fibril morphology ( J:236095 )

• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed

• AFM showed a large increase in height with swelling causing large jumps in profile analysis

• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure

skeleton

abnormal tendon collagen fibril morphology ( J:236095 )

• in tamoxifen-treated mice, atomic force (AFM) and scanning electron microscopy (SEM) of tail tendon collagen I revealed swollen and distorted fibrils, lack of cohesion, crimping and disordered fibrils, unlike in control mice where normal D-banding and consistently regular and aligned fibrils are observed

• AFM showed a large increase in height with swelling causing large jumps in profile analysis

• although the fibrillar D-banding period is not significantly altered, localized variations in the shape of the banding are observed, suggesting a disparity in quaternary collagen I structure

growth/size/body

growth/size/body region phenotype ( J:236095 )

N • no visceral abnormalities are observed after tamoxifen treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ARC syndrome		DOID:0050763	OMIM:PS208085	J:236095