All Phenotypes A1cf<+> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

A1cf⁺
wild type
MGI:3762960

Summary

60 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S/Sv * C57BL/6 * FVB/N	MGI:5523279
cn2	Cd36^tm2.1Mfe/Cd36^tm2.1Mfe A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	B6.Cg-Cd36^tm2.1Mfe A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}	MGI:5755142
cn3	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp	B6.Cg-Prdm16^tm1.1Brsp A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}	MGI:7314699
cn4	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Sdhaf4^em1Bcgen/Sdhaf4^em1Bcgen	B6.Cg-Sdhaf4^em1Bcgen A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}	MGI:7596078
cn5	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Clk4^em1Yihc/Clk4^em1Yihc	B6(FVB)-Clk4^em1Yihc A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}	MGI:7333095
cn6	Mybpc3^tm2.1Rmos/Mybpc3^tm2.1Rmos A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129 * C57BL/6 * FVB/N	MGI:5523783
cn7	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Ak2^em1.1Dze/Ak2^em1.1Dze	involves: 129 * C57BL/6 * FVB/N	MGI:6711700
cn8	Gt(ROSA)26Sor^{tm1.1(CAG-Mirc20)Eem}/Gt(ROSA)26Sor⁺ A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129 * C57BL/6 * FVB/N	MGI:5792842
cn9	Srf^tm1Zli/Srf^tm1Zli A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129 * C57BL/6J * FVB/N	MGI:5575856
cn10	Mcat^tm1.1Ssmi/Mcat^tm1.1Ssmi A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5466537
cn11	Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:6151153
cn12	Atp2a2^tm1.1Iemr/Atp2a2^tm1.1Iemr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129P2/OlaHsd * C57BL/6J * FVB/N	MGI:4441305
cn13	Atg7^tm1Tchi/Atg7^tm1Tchi Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj * FVB/N	MGI:6151155
cn14	Med1^tm2Jkr/Med1^tm2Jkr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129P2/OlaHsd * FVB/N	MGI:5911329
cn15	Ldb3^tm4Chen/Ldb3^tm4Chen A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S1/Sv * 129X1/SvJ * Black Swiss * FVB/N	MGI:3832390
cn16	Cacna1c^tm3Hfm/Cacna1c^tm4Hfm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5291995
cn17	Ryr2^tm1Krbr/Ryr2^tm1Krbr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5576935
cn18	Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5810170
cn19	Ryr2^tm1Krbr/Ryr2^tm3.1Swch A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5606049
cn20	Cacna1c^tm1Ggm/Cacna1c^tm1Ggm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5446618
cn21	Gt(ROSA)26Sor^{tm1(CAG-Nr2f2)Tsa}/Gt(ROSA)26Sor⁺ A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5906002
cn22	Eif4ebp1^tm1Nso/Eif4ebp1^tm1Nso Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJae * C57BL/6 * FVB/N	MGI:5810178
cn23	Txnip^tm1Rlee/Txnip^tm1Rlee A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJae * FVB/N	MGI:3818746
cn24	Pten^tm1Hwu/Pten^tm1Hwu A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJae * FVB/N	MGI:4882047
cn25	Mcu^tm1.1Jmol/Mcu^tm1.1Jmol A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5779906
cn26	Pik3cb^tm1.1Rzl/Pik3cb^tm1.1Rzl A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:4845868
cn27	Pik3ca^tm1.1Rzl/Pik3ca^tm1.1Rzl A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:4845867
cn28	Mcur1^{tm1c(KOMP)Wtsi}/Mcur1^{tm1c(KOMP)Wtsi} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJaeSor * C57BL/6N * FVB/N	MGI:5912149
cn29	Slc8b1^{tm1c(EUCOMM)Wtsi}/Slc8b1^{tm1c(EUCOMM)Wtsi} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S4/SvJaeSor * C57BL/6N * FVB/N	MGI:7316564
cn30	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Ppif^tm1Jmol/Ppif^tm1Jmol Slc8b1^{tm1c(EUCOMM)Wtsi}/Slc8b1^{tm1c(EUCOMM)Wtsi}	involves: 129S4/SvJaeSor * C57BL/6N * FVB/N	MGI:7316565
cn31	Cdh2^tm1Glr/Cdh2^{Gt(OST49160)Lex} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S5/SvEvBrd * 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:3580161
cn32	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5523280
cn33	Plce1^tm2Avsm/Plce1^tm2Avsm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5514169
cn34	Jup^tm1.1Glr/Jup^tm1.1Glr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL	MGI:4947241
cn35	Wdr1^tm1.1Zzy/Wdr1^tm1.1Zzy A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S6/SvEvTac * C57BL/6J	MGI:5688487
cn36	Cdh2^tm1Glr/Cdh2^tm1Hyn A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:3580162
cn37	Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S/Sv * C57BL/6 * FVB/N	MGI:5523277
cn38	Hcn4^tm1.1Ggc/Hcn4^tm1.1Ggc A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129S/SvEv * C57BL/6 * FVB/N	MGI:4888970
cn39	Myocd^tm1Msp/Myocd^tm1Msp A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129/Sv * C57BL/6J * FVB/N	MGI:5907042
cn40	Ctnna1^tm1Efu/Ctnna1^tm1Efu A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: 129X1/SvJ * FVB/N	MGI:5504499
cn41	Dmd^tm1.1Know/Dmd^tm1.1Know A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(Myh6-2A)#Know/0	involves: BALB/c * C3H * C57BL/6 * FVB/N	MGI:5569640
cn42	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(Myh6-2A)#Know/0	involves: BALB/c * C57BL/6 * FVB/N	MGI:5905888
cn43	Hspd1^{tm1c(EUCOMM)Hmgu}/Hspd1^{tm1c(EUCOMM)Hmgu} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: Black Swiss * C57BL/6 * C57BL/6N * FVB/N	MGI:6385859
cn44	Tspo^tm1.1Maf/Tspo^tm1.1Maf A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: C57BL/6 * FVB/N	MGI:5588664
cn45	Tnni3k^tm1Tfo/Tnni3k^tm1Tfo A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: C57BL/6 * FVB/N	MGI:5614265
cn46	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Pakap^tm1.1Div/Pakap^tm1.1Div	involves: C57BL/6 * FVB/N	MGI:7618341
cn47	Akap6^tm1.1Mskf/Akap6^tm1.1Mskf A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: C57BL/6 * FVB/N * SJL	MGI:5603568
cn48	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(CAG-cat,-Tcf25)1Xdgz/0	involves: C57BL/6J * FVB/N	MGI:7639760
cn49	Ppp1r12b^em1Chana/Ppp1r12b^em1Chana A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: C57BL/6J * FVB/N	MGI:7621837
cn50	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(CAG-cat,-Dusp14)4Lyg/0	involves: C57BL/6J * FVB/N	MGI:6197025
cn51	Rtf1^{tm1c(KOMP)Wtsi}/Rtf1^{tm1c(KOMP)Wtsi} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: C57BL/6N * FVB/N	MGI:7523000
cn52	Gt(ROSA)26Sor^{em1(Tbc1d15)Jren}/Gt(ROSA)26Sor^{em1(Tbc1d15)Jren} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: C57BL/6N * FVB/N	MGI:7645413
cn53	Tbc1d15^em1Jren/Tbc1d15^em1Jren A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: C57BL/6N * FVB/N	MGI:7645414
cn54	Irx3^tm3Hui/Irx3^tm3Hui Irx5^tm3Hui/Irx5^tm3Hui A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: FVB	MGI:5444495
cn55	Cxadr^tm1Mgot/Cxadr^tm1Mgot A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: FVB	MGI:3812384
cn56	Abcb8^tm1Hard/Abcb8^tm1Hard A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: FVB	MGI:5315861
cn57	A1cf^{Tg(Myh6-cre/Esr1)1Jmk}/A1cf⁺ Tg(CAG-DMPK)1323Coop/0	involves: FVB	MGI:5426794
cn58	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Dusp12^em1Zhzy/Dusp12^em1Zhzy	involves: FVB/N	MGI:7608005
cn59	Hif1a^tm1Stom/Hif1a^tm1Stom A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: FVB/N	MGI:3815316
cn60	Senp2^tm1.1Eyeh/Senp2^tm1.1Eyeh A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺	involves: FVB/N	MGI:5750664

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S/Sv * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)

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

cardiovascular system

abnormal myocardium layer morphology ( J:164749 )

• patchy interstitial mononuclear infiltration is observed at day 10, but resolves by 3 weeks; no myocyte hypertrophy is observed

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing

• marked transient systolic and diastolic depression occurs, with full recovery observed by 3 weeks after stopping tamoxifen treatment

muscle

abnormal myocardium layer morphology ( J:164749 )

• patchy interstitial mononuclear infiltration is observed at day 10, but resolves by 3 weeks; no myocyte hypertrophy is observed

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing

• marked transient systolic and diastolic depression occurs, with full recovery observed by 3 weeks after stopping tamoxifen treatment

Allelic Composition	Cd36^tm2.1Mfe/Cd36^tm2.1Mfe A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	B6.Cg-Cd36^tm2.1Mfe A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Cd36^tm2.1Mfe mutation (0 available); any Cd36 mutation (33 available)

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

homeostasis/metabolism

decreased cardiac muscle triglyceride level ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, ex vivo perfused working hearts show a significant reduction in myocardial triacylglycerol (TAG) content relative to control hearts

abnormal response to cardiac infarction ( J:225392 )

• following ischemia/reperfusion, ex vivo perfused working hearts from tamoxifen-treated mice display significantly improved myocardial functional recovery relative to control hearts, as shown by increased heart rate peak systolic pressure (HR PSP) and cardiac power compared to the pre-ischemic phase

• improved recovery is associated with lower calculated proton production prior to and following ischemia relative to control hearts

• during reperfusion, ATP production relative to cardiac work is dramatically reduced and myocardial lactate levels are significantly decreased, indicating increased post-ischemic cardiac efficiency relative to control hearts

decreased fatty acid oxidation ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, ex vivo perfused working hearts show a 48% reduction in FA (palmitate) oxidation rates relative to control hearts

abnormal glucose homeostasis ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, ex vivo perfused working hearts show a 68% increase in glucose oxidation rates, with no significant change in glycolytic rates relative to control hearts

• despite switch to increased mitochondrial oxidation of glucose versus FAs (53% of TCA cycle acetyl-CoA production versus 26% in controls), total TCA cycle acetyl-CoA production and total ATP production via exogenously supplied substrates are not significantly altered

decreased fatty acids level ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, ex vivo perfused working hearts display significantly decreased fatty acid (palmitate) uptake relative to control hearts

• however, serum concentrations of free FAs are not significantly altered

muscle

decreased cardiac muscle triglyceride level ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, ex vivo perfused working hearts show a significant reduction in myocardial triacylglycerol (TAG) content relative to control hearts

cardiovascular system

cardiovascular system phenotype ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, H&E staining showed normal cardiomyocyte morphology in apical heart sections

• ex vivo perfused working hearts show normal heart rate (HR), HR peak systolic pressure (PSP), cardiac power, cardiac output and coronary flow rates, as well as normal myocardial ATP, ADP, AMP, and phosphocreatine levels during aerobic perfusions

• in vivo, tamoxifen-treated hearts show normal baseline cardiac function with no detectable structural or morphological abnormalities

decreased cardiac muscle triglyceride level ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, ex vivo perfused working hearts show a significant reduction in myocardial triacylglycerol (TAG) content relative to control hearts

abnormal response to cardiac infarction ( J:225392 )

• improved recovery is associated with lower calculated proton production prior to and following ischemia relative to control hearts

cellular

decreased fatty acid oxidation ( J:225392 )

• at 4-6 weeks after tamoxifen treatment, ex vivo perfused working hearts show a 48% reduction in FA (palmitate) oxidation rates relative to control hearts

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp
Genetic Background	B6.Cg-Prdm16^tm1.1Brsp A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Prdm16^tm1.1Brsp mutation (1 available); any Prdm16 mutation (71 available)

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

cardiovascular system

cardiovascular system phenotype ( J:326525 )

N	• tamoxifen-treated mice do not show overt cardiac phenotypes, even 36 weeks after induction

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Sdhaf4^em1Bcgen/Sdhaf4^em1Bcgen
Genetic Background	B6.Cg-Sdhaf4^em1Bcgen A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Sdhaf4^em1Bcgen mutation (0 available); any Sdhaf4 mutation (6 available)

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

mortality/aging

premature death ( J:345348 )

• significantly reduced viability at 8 weeks after tamoxifen treatment

cardiovascular system

enlarged heart ( J:345348 )

• after tamoxifen treatment

growth/size/body

enlarged heart ( J:345348 )

• after tamoxifen treatment

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Clk4^em1Yihc/Clk4^em1Yihc
Genetic Background	B6(FVB)-Clk4^em1Yihc A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Clk4^em1Yihc mutation (0 available); any Clk4 mutation (35 available)

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

cardiovascular system

increased myocardial fiber size ( J:327369 )

• increased cross-sectional area without change in length in tamoxifen-treated mice

myocardium hypertrophy ( J:327369 )

• in tamoxifen-treated mice

• however, overexpression of a phosphorylation-mimic mutant of NEXN (S437E) rescues cardiac hypertrophy

increased heart weight ( J:327369 )

• in tamoxifen-treated mice

increased heart left ventricle size ( J:327369 )

• in tamoxifen-treated mice

cardiac interstitial fibrosis ( J:327369 )

• in tamoxifen-treated mice

• however, overexpression of a phosphorylation-mimic mutant of NEXN (S437E) rescues fibrosis

decreased heart ventricle muscle contractility ( J:327369 )

congestive heart failure ( J:327369 )

• rapid onset in tamoxifen-treated mice with decreased left ventricular internal diameter, diastole, and a significant decrease in the left ventricular ejection fraction

growth/size/body

myocardium hypertrophy ( J:327369 )

• in tamoxifen-treated mice

• however, overexpression of a phosphorylation-mimic mutant of NEXN (S437E) rescues cardiac hypertrophy

increased heart weight ( J:327369 )

• in tamoxifen-treated mice

increased lung weight ( J:327369 )

• in tamoxifen-treated mice

muscle

increased myocardial fiber size ( J:327369 )

• increased cross-sectional area without change in length in tamoxifen-treated mice

myocardium hypertrophy ( J:327369 )

• in tamoxifen-treated mice

• however, overexpression of a phosphorylation-mimic mutant of NEXN (S437E) rescues cardiac hypertrophy

decreased heart ventricle muscle contractility ( J:327369 )

abnormal sarcomere morphology ( J:327369 )

• disrupted integrity ruptured myofilaments, blurred Z-disk, and mitochondrial abnormalities in cardiomyocytes of tamoxifen-treated mice

diffuse Z line ( J:327369 )

• in cardiomyocytes of tamoxifen-treated mice

respiratory system

increased lung weight ( J:327369 )

• in tamoxifen-treated mice

cellular

cardiac interstitial fibrosis ( J:327369 )

• in tamoxifen-treated mice

• however, overexpression of a phosphorylation-mimic mutant of NEXN (S437E) rescues fibrosis

Allelic Composition	Mybpc3^tm2.1Rmos/Mybpc3^tm2.1Rmos A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129 * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Mybpc3^tm2.1Rmos mutation (0 available); any Mybpc3 mutation (41 available)

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

cardiovascular system

cardiovascular system phenotype ( J:202199 )

N	• gross cardiac morphology is normal 8 weeks after tamoxifen treatment

increased myocardial fiber size ( J:202199 )

• at 20 weeks in tamoxifen-treated mice

myocardial fiber disarray ( J:202199 )

• myocyte disarray in tamoxifen-treated mice 12 weeks after transaortic constriction

abnormal heart left ventricle morphology ( J:202199 )

• increased posterior wall thickness in diastole after 20 weeks of tamoxifen treatment

• increased left ventricle internal dimension in tamoxifen-treated mice after transaortic constriction

• however, internal dimension is normal after 20 weeks of tamoxifen treatment

cardiac fibrosis ( J:202199 )

• in tamoxifen-treated mice 12 weeks after transaortic constriction

cardiac interstitial fibrosis ( J:202199 )

• highly variable focal and diffuse 20 weeks after tamoxifen treatment

decreased heart ventricle muscle contractility ( J:202199 )

• decreased ejection fraction and isovolumic relaxation time in tamoxifen-treated mice

• reduced fractional shortening in tamoxifen-treated mice after transaortic constriction

• however, tamoxifen-treated mice exhibit normal left ventricle posterior wall thickness and left ventricle internal diameter

increased response of heart to induced stress ( J:202199 )

• following transaortic constriction, tamoxifen-treated mice exhibit increased left ventricle internal dimension and reduced fractional shortening compared with control mice

homeostasis/metabolism

increased response of heart to induced stress ( J:202199 )

• following transaortic constriction, tamoxifen-treated mice exhibit increased left ventricle internal dimension and reduced fractional shortening compared with control mice

muscle

increased myocardial fiber size ( J:202199 )

• at 20 weeks in tamoxifen-treated mice

myocardial fiber disarray ( J:202199 )

• myocyte disarray in tamoxifen-treated mice 12 weeks after transaortic constriction

decreased heart ventricle muscle contractility ( J:202199 )

• decreased ejection fraction and isovolumic relaxation time in tamoxifen-treated mice

• reduced fractional shortening in tamoxifen-treated mice after transaortic constriction

• however, tamoxifen-treated mice exhibit normal left ventricle posterior wall thickness and left ventricle internal diameter

cellular

cardiac interstitial fibrosis ( J:202199 )

• highly variable focal and diffuse 20 weeks after tamoxifen treatment

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Ak2^em1.1Dze/Ak2^em1.1Dze
Genetic Background	involves: 129 * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Ak2^em1.1Dze mutation (0 available); any Ak2 mutation (23 available)

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

cardiovascular system

dilated heart ventricle ( J:305579 )

• mice treated with tamoxifen at 6-8 weeks of age exhibit ventricular dilation, measured as an increase in end-diastolic and end-systolic volume, within 1-week post-induction

• cardiac chamber enlargement is transitory and recovers to pre-induction levels within 2 months

decreased heart left ventricle muscle contractility ( J:305579 )

• tamoxifen treated mice show a decrease in left ventricular ejection fraction within 1-week post-induction

• the reduced pump function is transitory and recovers to pre-induction levels within 2 months

abnormal heart echocardiography feature ( J:305579 )

• echocardiography shows an increase in end-diastolic and end-systolic volume and decreased left ventricular ejection fraction within 1-week post-tamoxifen induction

homeostasis/metabolism

abnormal metabolism ( J:305579 )

• tamoxifen-treated mice show increased fumarate and malate and the glycolytic metabolite glucose-6-phosophate in the myocardium

muscle

decreased heart left ventricle muscle contractility ( J:305579 )

• tamoxifen treated mice show a decrease in left ventricular ejection fraction within 1-week post-induction

• the reduced pump function is transitory and recovers to pre-induction levels within 2 months

Allelic Composition	Gt(ROSA)26Sor^{tm1.1(CAG-Mirc20)Eem}/Gt(ROSA)26Sor⁺ A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129 * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Gt(ROSA)26Sor^{tm1.1(CAG-Mirc20)Eem} mutation (0 available); any Gt(ROSA)26Sor mutation (1095 available)

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

cardiovascular system

abnormal myocardial fiber morphology ( J:233994 )

• 2 weeks after tamoxifen-treatment, the total number of cardiomyocytes and percentage of mononucleated cardiomyocytes compared with control mice

decreased myocardial fiber size ( J:233994 )

• 2 weeks after tamoxifen-treatment

increased myocardial fiber number ( J:233994 )

• 2 weeks after tamoxifen-treatment

increased heart weight ( J:233994 )

• increased heart weight to tibia length ratio 2 weeks after tamoxifen treatment

abnormal myocardial fiber physiology ( J:233994 )

• cardiomyocytes reenter the cell cycle 8 days after tamoxifen treatment

• increased cardiomyocytes proliferation in tamoxifen treated mice following induction of myocardial infarction

abnormal response to cardiac infarction ( J:233994 )

• following induced myocardial infarction, tamoxifen-treated mice exhibit reduced fibrotic scarring with increased myocardial tissue compared with control mice

• however, mice exhibit ventricular dilation and reduced fractional shortening and ejection fraction 3 weeks after injury

cellular

decreased cardiomyocyte apoptosis ( J:233994 )

• 8 days after tamoxifen treatment

homeostasis/metabolism

abnormal response to cardiac infarction ( J:233994 )

• following induced myocardial infarction, tamoxifen-treated mice exhibit reduced fibrotic scarring with increased myocardial tissue compared with control mice

• however, mice exhibit ventricular dilation and reduced fractional shortening and ejection fraction 3 weeks after injury

muscle

abnormal myocardial fiber morphology ( J:233994 )

• 2 weeks after tamoxifen-treatment, the total number of cardiomyocytes and percentage of mononucleated cardiomyocytes compared with control mice

decreased myocardial fiber size ( J:233994 )

• 2 weeks after tamoxifen-treatment

increased myocardial fiber number ( J:233994 )

• 2 weeks after tamoxifen-treatment

decreased cardiomyocyte apoptosis ( J:233994 )

• 8 days after tamoxifen treatment

growth/size/body

increased heart weight ( J:233994 )

• increased heart weight to tibia length ratio 2 weeks after tamoxifen treatment

Allelic Composition	Srf^tm1Zli/Srf^tm1Zli A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129 * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Srf^tm1Zli mutation (0 available); any Srf mutation (25 available)

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

mortality/aging

premature death ( J:135043 )

• all mice die 8 to 10 weeks after tamoxifen injection due to rapid progression to heart failure; mice appear sick and become inactive a few days before death

cardiovascular system

abnormal myocardium layer morphology ( J:135043 )

• following tamoxifen treatment, hearts show an irregular alignment of cardiomyocytes, with frequent gaps between cells

abnormal myocardial fiber morphology ( J:135043 )

• amount of polymerized F-actin in cardiomyocytes progressively decreases after tamoxifen treatment

• myofibrils at the intercalated disks are often stretched and fragmented following tamoxifen treatment

• Z disks of cardiomyocytes are misaligned and myofibrils are split 60 days after tamoxifen treatment

• 60 days after tamoxifen treatment, cardiac tissue shows a lower density of myofibrils and a defect in demarcation of Z lines and M lines

abnormal intercalated disk morphology ( J:135043 )

• 95% of intercalated disks of hearts are enlarged, irregularly shaped, and are thicker 60 days after tamoxifen treatment

• intercalated disks show extensive interdigitation and the presence of lacunae, a widened space at the site of myofibril attachment to the intercalated disks, following tamoxifen treatment

cardiac hypertrophy ( J:135043 )

• hearts show features of eccentric hypertrophy 2 months after tamoxifen treatment, with dilation of the ventricular chambers

• however, no concentric hypertrophy is seen

increased heart left ventricle size ( J:135043 )

• mild left ventricle enlargement is seen 1 month after tamoxifen treatment, without significant left atrium remodeling and moderately increased left ventricle mass index

dilated heart ventricle ( J:135043 )

• dilation of the ventricular chambers is seen 2 months after tamoxifen treatment

cardiac fibrosis ( J:135043 )

• mild fibrosis in subendocardial regions are seen 2 months after tamoxifen treatment

dilated cardiomyopathy ( J:135043 )

• hearts are enlarged 2 months after tamoxifen treatment, with impaired contractility and relaxation

• however, thickening of the free wall is not seen

decreased heart left ventricle muscle contractility ( J:135043 )

• decrease in left ventricular contractility is seen 21 days after tamoxifen treatment, with a decrease in ejection fraction and mean shortening velocity of circumferential fibers

• contractility and relaxation are moderately altered at 1 month after tamoxifen treatment, however 2 months after tamoxifen treatment, a massive decrease in left ventricle contractility and relaxation are seen, with increased E/Ea ratio, indicating heart failure

abnormal cardiac muscle relaxation ( J:135043 )

congestive heart failure ( J:135043 )

• heart failure is seen 8 to 10 weeks after tamoxifen treatment

muscle

abnormal myocardium layer morphology ( J:135043 )

• following tamoxifen treatment, hearts show an irregular alignment of cardiomyocytes, with frequent gaps between cells

abnormal myocardial fiber morphology ( J:135043 )

• amount of polymerized F-actin in cardiomyocytes progressively decreases after tamoxifen treatment

• myofibrils at the intercalated disks are often stretched and fragmented following tamoxifen treatment

• Z disks of cardiomyocytes are misaligned and myofibrils are split 60 days after tamoxifen treatment

• 60 days after tamoxifen treatment, cardiac tissue shows a lower density of myofibrils and a defect in demarcation of Z lines and M lines

abnormal intercalated disk morphology ( J:135043 )

• 95% of intercalated disks of hearts are enlarged, irregularly shaped, and are thicker 60 days after tamoxifen treatment

• intercalated disks show extensive interdigitation and the presence of lacunae, a widened space at the site of myofibril attachment to the intercalated disks, following tamoxifen treatment

dilated cardiomyopathy ( J:135043 )

• hearts are enlarged 2 months after tamoxifen treatment, with impaired contractility and relaxation

• however, thickening of the free wall is not seen

decreased heart left ventricle muscle contractility ( J:135043 )

• decrease in left ventricular contractility is seen 21 days after tamoxifen treatment, with a decrease in ejection fraction and mean shortening velocity of circumferential fibers

abnormal cardiac muscle relaxation ( J:135043 )

abnormal Z line morphology ( J:135043 )

• Z disks of cardiomyocytes are misaligned 60 days after tamoxifen treatment

growth/size/body

cardiac hypertrophy ( J:135043 )

• hearts show features of eccentric hypertrophy 2 months after tamoxifen treatment, with dilation of the ventricular chambers

• however, no concentric hypertrophy is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:135043

Allelic Composition	Mcat^tm1.1Ssmi/Mcat^tm1.1Ssmi A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Mcat^tm1.1Ssmi mutation (0 available); any Mcat mutation (13 available)

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

normal phenotype

no abnormal phenotype detected ( J:192213 )

• tamoxifen-treated mice appear normal

Allelic Composition	Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Cnot3^tm1.1Kjkb mutation (0 available); any Cnot3 mutation (34 available)

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

mortality/aging

premature death ( J:260012 )

• mice treated with tamoxifen at 3 months develop lethal heart failure

cardiovascular system

congestive heart failure ( J:260012 )

• mice treated with tamoxifen at 3 months develop lethal heart failure

Allelic Composition	Atp2a2^tm1.1Iemr/Atp2a2^tm1.1Iemr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129P2/OlaHsd * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Atp2a2^tm1.1Iemr mutation (0 available); any Atp2a2 mutation (74 available)

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

cardiovascular system

cardiovascular system phenotype ( J:157143 )

N	• tamoxifen-treated mice do not exhibit myocardial disarray or necrosis

abnormal heart left atrium morphology ( J:157143 )

• 4 and 7 weeks after tamoxifen treatment, left atrial diameter is increased compared to in Atp2a2^tm1.1Iemr homozygotes

dilated heart atrium ( J:157143 )

• after tamoxifen treatment

enlarged heart ( J:157143 )

• after tamoxifen treatment

abnormal cardiovascular system physiology ( J:157143 )

• tamoxifen-treated mice exhibit an increase in the time constant of isovolumetric pressure decay compared with Atp2a2^tm1.1Iemr homozygotes

• 7 weeks after tamoxifen treatment, mice exhibit diastolic dysfunction compared with Atp2a2^tm1.1Iemr homozygotes

decreased cardiac output ( J:157143 )

• 4 and 7 weeks after tamoxifen treatment

decreased cardiac muscle contractility ( J:157143 )

• 4 weeks after tamoxifen treatment, mice exhibit reduced contractile function compared with Atp2a2^tm1.1Iemr homozygotes as determined by Doppler imaging

• at low stimulation frequency, cardiomyocytes from tamoxifen-treated mice exhibit reduced contraction magnitude compared with similarly treated cardiomyocytes from Atp2a2^tm1.1Iemr homozygotes

• 7 weeks after tamoxifen treatment, fractional shortening is reduced compared to in Atp2a2^tm1.1Iemr homozygotes

• 4 and 7 weeks after tamoxifen treatment, end-diastolic pressure compared to in Atp2a2^tm1.1Iemr homozygotes

abnormal heart left ventricle pressure ( J:157143 )

• 4 and 7 weeks after tamoxifen treatment, mice exhibit reduced maximum positive and minimum derivatives of the left ventricular pressure compared with Atp2a2^tm1.1Iemr homozygotes

decreased heart rate ( J:157143 )

• 4 and 7 weeks after tamoxifen treatment, anesthetized mice exhibit decreased heart rate compared with Atp2a2^tm1.1Iemr homozygotes

abnormal myocardial fiber physiology ( J:157143 )

• cardiomyocytes from tamoxifen-treated mice exhibit reduced magnitude of calcium ion transients and prolonged time to half decay of calcium ion transients compared with similarly treated cardiomyocytes from Atp2a2^tm1.1Iemr homozygotes

• when stimulated at a 6 Hz frequency, cardiomyocytes from tamoxifen-treated mice exhibit shorter diastolic sarcomere length and a greater increase in the contractile response per unit during systole compared with similarly treated cardiomyocytes from Atp2a2^tm1.1Iemr homozygotes

• during the slow decline of caffeine transients in the presence of nickel ions, cardiomyocytes from tamoxifen-treated mice exhibit shorter sarcomere length compared with similarly treated cardiomyocytes from Atp2a2^tm1.1Iemr homozygotes

• 4 weeks after tamoxifen treatment, cardiomyocytes exhibit reduced sarcoplasmic reticulum calcium ion content compared with cardiomyocytes from Atp2a2^tm1.1Iemr homozygotes

• 7 weeks after treatment with tamoxifen, mice exhibit reduced maximal rate of cardiomyocyte relaxation compared with Atp2a2^tm1.1Iemr homozygotes

decreased systemic arterial systolic blood pressure ( J:157143 )

• 7 weeks after tamoxifen treatment

homeostasis/metabolism

increased circulating noradrenaline level ( J:157143 )

• in tamoxifen-treated mice at 4 and 7 weeks

muscle

decreased cardiac muscle contractility ( J:157143 )

• 4 weeks after tamoxifen treatment, mice exhibit reduced contractile function compared with Atp2a2^tm1.1Iemr homozygotes as determined by Doppler imaging

• at low stimulation frequency, cardiomyocytes from tamoxifen-treated mice exhibit reduced contraction magnitude compared with similarly treated cardiomyocytes from Atp2a2^tm1.1Iemr homozygotes

• 7 weeks after tamoxifen treatment, fractional shortening is reduced compared to in Atp2a2^tm1.1Iemr homozygotes

• 4 and 7 weeks after tamoxifen treatment, end-diastolic pressure compared to in Atp2a2^tm1.1Iemr homozygotes

growth/size/body

enlarged heart ( J:157143 )

• after tamoxifen treatment

Allelic Composition	Atg7^tm1Tchi/Atg7^tm1Tchi Cnot3^tm1.1Kjkb/Cnot3^tm1.1Kjkb A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Atg7^tm1Tchi mutation (3 available); any Atg7 mutation (51 available)
Cnot3^tm1.1Kjkb mutation (0 available); any Cnot3 mutation (34 available)

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

mortality/aging

premature death ( J:260012 )

• tamoxifen-treated mice survive until P40

cardiovascular system

decreased cardiac muscle contractility ( J:260012 )

• not as severe as in mice Cnot3^tm2.1Tya A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mice

muscle

decreased cardiac muscle contractility ( J:260012 )

• not as severe as in mice Cnot3^tm2.1Tya A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mice

Allelic Composition	Med1^tm2Jkr/Med1^tm2Jkr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129P2/OlaHsd * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Med1^tm2Jkr mutation (0 available); any Med1 mutation (81 available)

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

The Med1^tm2Jkr/Med1^tm2Jkr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ mouse heart is flaccid and flabby after tamoxifen induction.

mortality/aging

premature death ( J:243730 )

• mice survive between 13 and 28 days after the first day of tamoxifen injection

cardiovascular system

abnormal heart morphology ( J:243730 )

• hearts appear increasingly flaccid by 14 days after first tamoxifen injection

enlarged heart ( J:243730 )

• mice treated with tamoxifen at 7 weeks of age exhibit an increase in heart size by 14 days after first tamoxifen injection

thin ventricular wall ( J:243730 )

• tamoxifen treated mice show thinning of the ventricular walls

dilated heart ventricle ( J:243730 )

• tamoxifen treated mice show dilatation of the right and left ventricular chambers with thinning of the walls and myocardial cells

cardiac interstitial fibrosis ( J:243730 )

• interstitial myocardial fibrosis in tamoxifen-treated hearts

dilated cardiomyopathy ( J:243730 )

decreased cardiac muscle contractility ( J:243730 )

• tamoxifen-treated mice show diminished heart contractility with ejection fraction only 11% vs. 64% in controls and fractional shortening of 4.77% vs. 33.88% in controls

abnormal heart echocardiography feature ( J:243730 )

• echocardiography indicates increased left ventricular end-diastolic internal dimension, and decreased fractional shortening and ejection fraction in tamoxifen treated mice

congestive heart failure ( J:243730 )

• in tamoxifen treated mice

cellular

cardiac interstitial fibrosis ( J:243730 )

• interstitial myocardial fibrosis in tamoxifen-treated hearts

increased cardiomyocyte apoptosis ( J:243730 )

• tamoxifen-treated hearts show enhanced apoptosis, with the number of apoptotic cardiomyocytes increased about 10-fold

muscle

dilated cardiomyopathy ( J:243730 )

decreased cardiac muscle contractility ( J:243730 )

• tamoxifen-treated mice show diminished heart contractility with ejection fraction only 11% vs. 64% in controls and fractional shortening of 4.77% vs. 33.88% in controls

increased cardiomyocyte apoptosis ( J:243730 )

• tamoxifen-treated hearts show enhanced apoptosis, with the number of apoptotic cardiomyocytes increased about 10-fold

growth/size/body

enlarged heart ( J:243730 )

• mice treated with tamoxifen at 7 weeks of age exhibit an increase in heart size by 14 days after first tamoxifen injection

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
congestive heart failure	DOID:6000		J:243730
dilated cardiomyopathy	DOID:12930	OMIM:PS115200	J:243730

Allelic Composition	Ldb3^tm4Chen/Ldb3^tm4Chen A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * Black Swiss * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Ldb3^tm4Chen mutation (0 available); any Ldb3 mutation (44 available)

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

mortality/aging

premature death ( J:144739 )

• all mice die between 1 and 16 weeks after tamoxifen treatment

cardiovascular system

enlarged heart ( J:144739 )

• after tamoxifen treatment

dilated heart left ventricle ( J:144739 )

• both ventricles are severely dilated after tamoxifen treatment

dilated heart right ventricle ( J:144739 )

• both ventricles are severely dilated after tamoxifen treatment

abnormal cardiovascular system physiology ( J:144739 )

• decreased heart function one month after tamoxifen treatment

dilated cardiomyopathy ( J:144739 )

• after tamoxifen treatment

muscle

dilated cardiomyopathy ( J:144739 )

• after tamoxifen treatment

growth/size/body

enlarged heart ( J:144739 )

• after tamoxifen treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1C		DOID:0110423	OMIM:601493	J:144739

Allelic Composition	Cacna1c^tm3Hfm/Cacna1c^tm4Hfm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Cacna1c^tm3Hfm mutation (1 available); any Cacna1c mutation (147 available)
Cacna1c^tm4Hfm mutation (0 available); any Cacna1c mutation (147 available)

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

mortality/aging

premature death ( J:175463 )

• mice die within 3 weeks of tamoxifen treatment

muscle

abnormal muscle electrophysiology ( J:175463 )

• vetricular cardiomyocytes from tamoxifen-treated mice exhibit reduced current-voltage relation of current compared with cells from control mice

Allelic Composition	Ryr2^tm1Krbr/Ryr2^tm1Krbr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Ryr2^tm1Krbr mutation (1 available); any Ryr2 mutation (328 available)

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

mortality/aging

premature death ( J:210083 )

• tamoxifen-treated mice exhibit sudden cardiac death

cardiovascular system

decreased cardiac output ( J:210083 )

• in tamoxifen-treated mice

• however, compensatory mechanisms transiently ameliorate detrimental effects

abnormal sinus arrhythmia ( J:210083 )

• severe in tamoxifen-treated mice

decreased heart rate ( J:210083 )

• in tamoxifen-treated mice

sinus bradycardia ( J:210083 )

• in tamoxifen-treated mice

increased heart rate ( J:210083 )

• repetitive episodes of tachycardic arrhythmia in tamoxifen-treated mice

atrioventricular block ( J:210083 )

• secondary in tamoxifen-treated mice

abnormal T wave ( J:210083 )

• distinct T wave in tamoxifen-treated mice

cardiomyopathy ( J:210083 )

• in tamoxifen-treated mice

congestive heart failure ( J:210083 )

• in tamoxifen-treated mice

behavior/neurological

lethargy ( J:210083 )

• 4 days after tamoxifen treatment

homeostasis/metabolism

abnormal atrial thrombosis ( J:210083 )

• in tamoxifen-treated mice

muscle

cardiomyopathy ( J:210083 )

• in tamoxifen-treated mice

Allelic Composition	Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Mtor^tm1.1Gcon mutation (1 available); any Mtor mutation (115 available)

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

Enlarged hearts with thinned ventricular walls and enlarged cardiac chambers in Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice

mortality/aging

premature death ( J:163763 )

• mice start dying at 4 weeks after tamoxifen (TMX) administration; the median survival age is 6 weeks and no mice survive for >8 weeks

growth/size/body

enlarged heart ( J:163763 )

• at 4 weeks after TMX treatment, mice exhibit significantly enlarged hearts relative to controls

cardiovascular system

abnormal myocardial fiber morphology ( J:163763 )

• at 2 weeks after TMX treatment, LV myocardium exhibits sarcomeric disarray and swollen mitochondria, unlike in control hearts

decreased myocardial fiber size ( J:163763 )

• at 2 weeks after TMX treatment, cross-sectional area of cardiomyocytes is reduced relative to that in control mice

• adult cardiomyocytes isolated from TMX-treated mice are significantly thinner and shorter than those of control mice

increased heart atrium size ( J:163763 )

• atrial chambers are enlarged at 4 weeks after TMX treatment

thin interventricular septum ( J:163763 )

• interventricular septum is thinner than normal at 4 weeks after TMX treatment

enlarged heart ( J:163763 )

• at 4 weeks after TMX treatment, mice exhibit significantly enlarged hearts relative to controls

decreased heart left ventricle wall thickness ( J:163763 )

• left ventricle (LV) wall is thinner than normal at 4 weeks after TMX treatment

increased heart ventricle size ( J:163763 )

• ventricular chambers are enlarged at 4 weeks after TMX treatment

cardiac interstitial fibrosis ( J:163763 )

• at 4 weeks after TMX treatment, mice show increased interstitial fibrosis in the LV and interventricular septum relative to controls

• the cardiac fibrotic index is already increased at 1 week after TMX treatment and becomes significantly increased thereafter

dilated cardiomyopathy ( J:163763 )

• TMX-treated mice develop lethal dilated cardiomyopathy

decreased cardiac muscle contractility ( J:163763 )

• TMX-treated mice show markedly lower basal inotropy and lusitropy and only very weak reactivity to stimulation with increasing units of dobutamine

decreased heart ventricle muscle contractility ( J:163763 )

• at 4 weeks after TMX treatment, LV fractional shortening percentage (LVFS %) is significantly reduced relative to that in controls

abnormal myocardial fiber physiology ( J:163763 )

• in culture, adult ventricular myocytes isolated from TMX-treated mice show significantly reduced protein synthesis relative to controls, as assessed by a [³H]leucine uptake assay

• TMX-treated mice show a progressive (2- to 8-fold) increase in the expression of cardiac fetal genes (Nppa, Myh7, Acta1) relative to controls at 2 weeks and 4 weeks post-TMX

• TMX-treated mice show a progressive reduction in cytochrome c oxidase subunit IV (CoxIV) expression, indicating a loss in the oxidative capacity of myocardial mitochondria

increased response of heart to induced stress ( J:163763 )

• at 2 weeks after transverse aortic constriction (TAC), i.e. 3 weeks post-TMX treatment, mice show an impaired hypertrophic response and accelerated heart failure progression, as determined by a significantly reduced increase in LV wall thickness, a more dilated LV chamber, a significantly reduced ratio of LV weight- and heart weight-to-tibial length, accelerated contractile dysfunction, reduced induction of cardiac fetal genes, and significantly reduced survival relative to control TAC mice, with a 40% death rate already noted after 1 week of TAC

congestive heart failure ( J:163763 )

• at 4 weeks after TMX treatment, mice exhibit heart failure, as assessed by echocardiography and the dobutamine stress test

• however, cardiac function is maintained up to 2-3 weeks after TMX treatment

cellular

cardiac interstitial fibrosis ( J:163763 )

• at 4 weeks after TMX treatment, mice show increased interstitial fibrosis in the LV and interventricular septum relative to controls

• the cardiac fibrotic index is already increased at 1 week after TMX treatment and becomes significantly increased thereafter

dilated mitochondrion ( J:163763 )

• at 2 weeks after TMX treatment, LV myocardium exhibits swollen mitochondria, unlike in control hearts

abnormal autophagy ( J:163763 )

• at 1 week after TMX treatment, cardiac expression of several autophagy-related proteins is increased and autophagic bodies are observed in the myocardium, unlike in control hearts

increased cardiomyocyte apoptosis ( J:163763 )

• TMX-treated mice show a progressive and severe loss of cardiomyocytes due to apoptosis, as shown by TUNEL staining

• at 4 weeks after TMX treatment, cleaved Parp expression is significantly increased in the heart relative to that in control mice

abnormal mitochondrial physiology ( J:163763 )

• TMX-treated mice show a progressive reduction in cytochrome c oxidase subunit IV (CoxIV) expression, indicating reduced oxidative capacity of myocardial mitochondria

abnormal translation ( J:163763 )

• in culture, adult ventricular myocytes isolated from TMX-treated mice show significantly reduced protein synthesis relative to controls, as assessed by a [³H]leucine uptake assay

homeostasis/metabolism

increased response of heart to induced stress ( J:163763 )

abnormal autophagy ( J:163763 )

• at 1 week after TMX treatment, cardiac expression of several autophagy-related proteins is increased and autophagic bodies are observed in the myocardium, unlike in control hearts

abnormal translation ( J:163763 )

• in culture, adult ventricular myocytes isolated from TMX-treated mice show significantly reduced protein synthesis relative to controls, as assessed by a [³H]leucine uptake assay

ascites ( J:163763 )

• TMX-treated mice develop ascites

pleural effusion ( J:163763 )

• TMX-treated mice exhibit pleural effusions

muscle

abnormal myocardial fiber morphology ( J:163763 )

• at 2 weeks after TMX treatment, LV myocardium exhibits sarcomeric disarray and swollen mitochondria, unlike in control hearts

decreased myocardial fiber size ( J:163763 )

• at 2 weeks after TMX treatment, cross-sectional area of cardiomyocytes is reduced relative to that in control mice

• adult cardiomyocytes isolated from TMX-treated mice are significantly thinner and shorter than those of control mice

dilated cardiomyopathy ( J:163763 )

• TMX-treated mice develop lethal dilated cardiomyopathy

decreased cardiac muscle contractility ( J:163763 )

• TMX-treated mice show markedly lower basal inotropy and lusitropy and only very weak reactivity to stimulation with increasing units of dobutamine

decreased heart ventricle muscle contractility ( J:163763 )

• at 4 weeks after TMX treatment, LV fractional shortening percentage (LVFS %) is significantly reduced relative to that in controls

increased cardiomyocyte apoptosis ( J:163763 )

• TMX-treated mice show a progressive and severe loss of cardiomyocytes due to apoptosis, as shown by TUNEL staining

• at 4 weeks after TMX treatment, cleaved Parp expression is significantly increased in the heart relative to that in control mice

abnormal sarcomere morphology ( J:163763 )

• at 2 weeks after TMX treatment, LV myocardium exhibits sarcomeric disarray, unlike in control hearts

respiratory system

pleural effusion ( J:163763 )

• TMX-treated mice exhibit pleural effusions

Allelic Composition	Ryr2^tm1Krbr/Ryr2^tm3.1Swch A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * FVB/N

Find Mice

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

mortality/aging

premature death ( J:215190 )

• mice die starting around 11 days post tamoxifen injection, with most dying by day 14

cardiovascular system

decreased heart rate ( J:215190 )

• 12 days post tamoxifen treatment, mice exhibit a reduced basal heart rate

• tamoxifen treated mice, however, do not exhibit stress-induced (by caffeine or epinephrine) ventricular tachyarrhythmias at young or older ages

Allelic Composition	Cacna1c^tm1Ggm/Cacna1c^tm1Ggm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Cacna1c^tm1Ggm mutation (0 available); any Cacna1c mutation (147 available)

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

mortality/aging

premature death ( J:189406 )

• average survival time of 11.9 +/- 3 days following tamoxifen treatment for 5 days

cardiovascular system

dilated heart ventricle ( J:189406 )

• increase in ventricular end diastolic volume after tamoxifen treatment

decreased cardiac muscle contractility ( J:189406 )

• profound decrease in myocardial contractility, as assessed by fractional shortening, after tamoxifen treatment

muscle

decreased cardiac muscle contractility ( J:189406 )

• profound decrease in myocardial contractility, as assessed by fractional shortening, after tamoxifen treatment

Allelic Composition	Gt(ROSA)26Sor^{tm1(CAG-Nr2f2)Tsa}/Gt(ROSA)26Sor⁺ A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Gt(ROSA)26Sor^{tm1(CAG-Nr2f2)Tsa} mutation (0 available); any Gt(ROSA)26Sor mutation (1095 available)

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

mortality/aging

premature death ( J:227012 )

• tamoxifen-treated mice show increased mortality

cardiovascular system

enlarged heart ( J:227012 )

• tamoxifen-treated mice develop greatly enlarged heart 16 days after induction

abnormal cardiovascular system physiology ( J:227012 )

• tamoxifen-treated mice exhibit impaired cardiac fuel utilization

dilated cardiomyopathy ( J:227012 )

• tamoxifen-treated mice develop dilated cardiomyopathy, showing increased left ventricular interior dimension, reduced fractional shortening, and decreased relative wall thickness

decreased cardiac muscle contractility ( J:227012 )

• 16 days after induction with tamoxifen, mice exhibit contractile dysfunction analogous to end-stage dilated cardiomyopathy

cellular

abnormal mitochondrial inner membrane morphology ( J:227012 )

• mitochondria exhibit increased distance between cristae in the heart 9 days after induction with tamoxifen

abnormal mitochondrial shape ( J:227012 )

• mitochondria exhibit a round in the heart 9 days after induction with tamoxifen

abnormal cell physiology ( J:227012 )

• tamoxifen-treated hearts exhibit reduced glucose oxidation rates ex vivo

abnormal mitochondrial physiology ( J:227012 )

• reduction of enzyme activities of complexes I, II, III, and IV is isolated mitochondria of ventricles from tamoxifen-treated mice

• mitochondrial protein function is compromised in hearts of tamoxifen-treated mice, with a reduction of mitochondrial aconitase activity

• however, the number and density of mitochondria are normal in hearts

abnormal respiratory electron transport chain ( J:227012 )

• mitochondrial respiration rate is lower in heart 4 days after induction with tamoxifen when cardiac dysfunction is not yet observed

abnormal oxidative phosphorylation ( J:227012 )

• higher levels of oxidized proteins are seen in heart mitochondria of day 9 of induction with tamoxifen

• decrease of mitochondrial oxygen consumption rate and lower mitochondrial ATP content in hearts of tamoxifen-treated mice, suggesting a reduction in oxidative phosphorylation capacity and ATP production in mitochondria

decreased fatty acid oxidation ( J:227012 )

• tamoxifen-treated hearts exhibit a lower oleate oxidation rate ex vivo

homeostasis/metabolism

decreased fatty acid oxidation ( J:227012 )

• tamoxifen-treated hearts exhibit a lower oleate oxidation rate ex vivo

decreased oxygen consumption ( J:227012 )

• tamoxifen-treated hearts show decreased oxygen consumption rate

muscle

dilated cardiomyopathy ( J:227012 )

• tamoxifen-treated mice develop dilated cardiomyopathy, showing increased left ventricular interior dimension, reduced fractional shortening, and decreased relative wall thickness

decreased cardiac muscle contractility ( J:227012 )

• 16 days after induction with tamoxifen, mice exhibit contractile dysfunction analogous to end-stage dilated cardiomyopathy

growth/size/body

enlarged heart ( J:227012 )

• tamoxifen-treated mice develop greatly enlarged heart 16 days after induction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:227012

Allelic Composition	Eif4ebp1^tm1Nso/Eif4ebp1^tm1Nso Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJae * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Eif4ebp1^tm1Nso mutation (2 available); any Eif4ebp1 mutation (32 available)
Mtor^tm1.1Gcon mutation (1 available); any Mtor mutation (115 available)

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

mortality/aging

premature death ( J:163763 )

• after tamoxifen (TMX) treatment, mice exhibit significantly enhanced survival relative to Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice

cardiovascular system

cardiovascular system phenotype ( J:163763 )

N	• at 4 weeks after TMX treatment, mice exhibit normal echocardiographic parameters, cardiomyocyte size, and cardiac function (as assessed by the LV fractional shortening %)

cardiac interstitial fibrosis ( J:163763 )

• at 4 weeks after TMX treatment, mice show significantly reduced fibrosis relative to Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice

cellular

cardiac interstitial fibrosis ( J:163763 )

• at 4 weeks after TMX treatment, mice show significantly reduced fibrosis relative to Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice

abnormal autophagy ( J:163763 )

• after TMX treatment, mice show a similar expression of autophagy genes relative to Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice, suggesting that autophagy is not involved in the amelioration of the heart failure phenotype

decreased cardiomyocyte apoptosis ( J:163763 )

• at 4 weeks after TMX treatment, mice show a significant decrease of cleaved Parp protein and TUNEL+ cells in the myocardium relative to Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice

abnormal mitochondrial physiology ( J:163763 )

• at 4 weeks after TMX treatment, mice show increased cytochrome c oxidase subunit IV (CoxIV) expression in heart lysates relative to Mtor^tm1.1Gcon/Mtor^tm1.1Gcon A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice, suggesting that mitochondrial function is improved

muscle

decreased cardiomyocyte apoptosis ( J:163763 )

homeostasis/metabolism

abnormal autophagy ( J:163763 )

Allelic Composition	Txnip^tm1Rlee/Txnip^tm1Rlee A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJae * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Txnip^tm1Rlee mutation (1 available); any Txnip mutation (48 available)

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

cardiovascular system

increased cardiac muscle cell glucose uptake ( J:141487 )

• robust increase in glucose uptake in 4-hydroxytamoxifen treated mice compared to controls

abnormal response of heart to induced stress ( J:141487 )

• mice treated with 4-hydroxytamoxifen to induce recombination display a decrease in pressure overload induced progressive hypertrophy during the early phase compared to controls

muscle

increased cardiac muscle cell glucose uptake ( J:141487 )

• robust increase in glucose uptake in 4-hydroxytamoxifen treated mice compared to controls

homeostasis/metabolism

abnormal response of heart to induced stress ( J:141487 )

• mice treated with 4-hydroxytamoxifen to induce recombination display a decrease in pressure overload induced progressive hypertrophy during the early phase compared to controls

cellular

increased cardiac muscle cell glucose uptake ( J:141487 )

• robust increase in glucose uptake in 4-hydroxytamoxifen treated mice compared to controls

Allelic Composition	Pten^tm1Hwu/Pten^tm1Hwu A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJae * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Pten^tm1Hwu mutation (17 available); any Pten mutation (87 available)

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

cardiovascular system

abnormal response to cardiac infarction ( J:149180 )

• hearts of mutants treated with tamoxifen for 3 weeks to induce cre-expression develop significantly better function recovery in response to 30 min ischemia followed by 120 min reperfusion than controls, showing significantly improved end-diastolic pressure, left ventricle developed pressure (LVDP) and LVDP recoveries, and improved systolic and diastolic contractility of hearts

• at 60 min post reperfusion, recovery of left ventricular diastolic pressure reaches 77.9% of pre-ischemia in hearts versus 44% in controls

• hearts have significantly fewer apoptosis positive cardiomyocytes after ischemia/reperfusion (I/R) injury than controls

decreased myocardial infarct size ( J:149180 )

• mutants treated with tamoxifen to induce cre-expression exhibit a significant reduction in infarct size after ischemia

homeostasis/metabolism

abnormal response to cardiac infarction ( J:149180 )

• at 60 min post reperfusion, recovery of left ventricular diastolic pressure reaches 77.9% of pre-ischemia in hearts versus 44% in controls

• hearts have significantly fewer apoptosis positive cardiomyocytes after ischemia/reperfusion (I/R) injury than controls

decreased myocardial infarct size ( J:149180 )

• mutants treated with tamoxifen to induce cre-expression exhibit a significant reduction in infarct size after ischemia

Allelic Composition	Mcu^tm1.1Jmol/Mcu^tm1.1Jmol A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Mcu^tm1.1Jmol mutation (2 available); any Mcu mutation (26 available)

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

cardiovascular system

cardiovascular system phenotype ( J:224853 )

N	• hearts of tamoxifen-treated mice exhibit normal cardiac adaptation to long-term stress induced by transverse aortic constriction

abnormal myocardial fiber morphology ( J:224853 )

• tamoxifen-treated mice exhibit inhibited acute cardiac mitochondrial calcium uptake compared with control cells

• at 18 weeks, cardiac myocytes from tamoxifen-treated mice challenged with calcium exhibit a severely blunted compared with control cells

• cardiac myocytes from tamoxifen-treated mice exhibit lower sodium-induced calcium efflux rates compared with control cells

• cardiac mitochondria from mice treated with tamoxifen and dobutamine fail to exhibit an increase in calcium unlike control mitochondria

• however, mice exhibit normal baseline mitochondrial calcium levels, response to Ru360, and elevated calcium levels in the mitochondrial following sustained dobutamine treatment

decreased heart ventricle muscle contractility ( J:224853 )

• tamoxifen-treated mice subjected to dobutamine (the beta-adrenergic receptor agonist) exhibit lesser short-term increase in the maximal rate of cardiac pressure compared with control mice

• however, sustained administration of dobutamine at 32 ng/g/min induced similar ventricular pressure

abnormal myocardial fiber physiology ( J:224853 )

• cardiomyocytes from tamoxifen treated mice fail to exhibit an increase in mitochondrial oxygen consumption and ATP utilization compared with control mice

• however, baseline mitochondrial oxygen consumption and ATP utilization are normal

decreased myocardial infarct size ( J:224853 )

• in tamoxifen treated mice

homeostasis/metabolism

decreased aerobic running capacity ( J:224853 )

• under the short warm-up/high-intensity sprinting regimen, tamoxifen-treated mice exhibit reduced running capacity compared with control mice

• however, the difference is lost with a longer warm-up period

decreased myocardial infarct size ( J:224853 )

• in tamoxifen treated mice

behavior/neurological

decreased aerobic running capacity ( J:224853 )

• under the short warm-up/high-intensity sprinting regimen, tamoxifen-treated mice exhibit reduced running capacity compared with control mice

• however, the difference is lost with a longer warm-up period

cellular

decreased cardiomyocyte apoptosis ( J:224853 )

• in cardiomyocytes from tamoxifen treated mice in response to ionomycin

muscle

abnormal myocardial fiber morphology ( J:224853 )

• tamoxifen-treated mice exhibit inhibited acute cardiac mitochondrial calcium uptake compared with control cells

• at 18 weeks, cardiac myocytes from tamoxifen-treated mice challenged with calcium exhibit a severely blunted compared with control cells

• cardiac myocytes from tamoxifen-treated mice exhibit lower sodium-induced calcium efflux rates compared with control cells

• cardiac mitochondria from mice treated with tamoxifen and dobutamine fail to exhibit an increase in calcium unlike control mitochondria

• however, mice exhibit normal baseline mitochondrial calcium levels, response to Ru360, and elevated calcium levels in the mitochondrial following sustained dobutamine treatment

decreased heart ventricle muscle contractility ( J:224853 )

• tamoxifen-treated mice subjected to dobutamine (the beta-adrenergic receptor agonist) exhibit lesser short-term increase in the maximal rate of cardiac pressure compared with control mice

• however, sustained administration of dobutamine at 32 ng/g/min induced similar ventricular pressure

decreased cardiomyocyte apoptosis ( J:224853 )

• in cardiomyocytes from tamoxifen treated mice in response to ionomycin

Allelic Composition	Pik3cb^tm1.1Rzl/Pik3cb^tm1.1Rzl A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Pik3cb^tm1.1Rzl mutation (0 available); any Pik3cb mutation (150 available)

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

cardiovascular system

cardiovascular system phenotype ( J:166421 )

N	• in tamoxifen-treated mice exhibit normal myocyte reduced inward calcium ion current density

decreased heart weight ( J:166421 )

• slightly in tamoxifen-treated mice

Allelic Composition	Pik3ca^tm1.1Rzl/Pik3ca^tm1.1Rzl A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Pik3ca^tm1.1Rzl mutation (0 available); any Pik3ca mutation (65 available)

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

cardiovascular system

decreased heart weight ( J:166421 )

• in tamoxifen-treated mice

increased heart left ventricle size ( J:166421 )

• mildly in tamoxifen-treated mice

thick ventricular wall ( J:166421 )

• posterior wall thickness in tamoxifen-treated mice is slightly decreased compared to in wild-type mice

decreased cardiac muscle contractility ( J:166421 )

• in tamoxifen-treated mice

abnormal myocardial fiber physiology ( J:166421 )

• myocytes of tamoxifen-treated mice exhibit reduced inward calcium ion current density compared with wild-type cells

muscle

decreased cardiac muscle contractility ( J:166421 )

• in tamoxifen-treated mice

Allelic Composition	Mcur1^{tm1c(KOMP)Wtsi}/Mcur1^{tm1c(KOMP)Wtsi} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6N * FVB/N
Cell Lines	EPD0332_3_A12

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Mcur1^{tm1c(KOMP)Wtsi} mutation (0 available); any Mcur1 mutation (20 available)

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:235756 )

• some mice die by 3 weeks of age

• however, some mice are viable

cellular

abnormal mitochondrial physiology ( J:235756 )

• cardiomyocyte mitochondria exhibit almost no calcium uptake in response to extramitochondrial calcium ion pulses unlike control cells

• cardiomyocytes mitochondria exhibit defective inward mitochondrial calcium ion uniporter-dependent inward current compared with control cells

• however, mitochondrial membrane potential is normal

growth/size/body

decreased body size ( J:235756 )

Allelic Composition	Slc8b1^{tm1c(EUCOMM)Wtsi}/Slc8b1^{tm1c(EUCOMM)Wtsi} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6N * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Slc8b1^{tm1c(EUCOMM)Wtsi} mutation (1 available); any Slc8b1 mutation (45 available)

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

mortality/aging

premature death ( J:325413 )

• most mice died within two weeks of tamoxifen treatment

cardiovascular system

increased myocardial fiber size ( J:325413 )

• increased cross-sectional area post tamoxifen-treatment

increased heart weight ( J:325413 )

• post tamoxifen-treatment

cardiac hypertrophy ( J:325413 )

• post tamoxifen-treatment

dilated heart left ventricle ( J:325413 )

• 3 days post tamoxifen-treatment

cardiac fibrosis ( J:325413 )

• post tamoxifen-treatment

decreased heart left ventricle muscle contractility ( J:325413 )

• decreased left ventricular function 3 days post tamoxifen-treatment as measured by fractional shortening and left ventricular end-diastolic dimension

decreased heart rate ( J:325413 )

• post tamoxifen-treatment

irregular heartbeat ( J:325413 )

• post tamoxifen-treatment only immediately before sinus arrest

prolonged PR interval ( J:325413 )

• post tamoxifen-treatment

prolonged QRS complex duration ( J:325413 )

• post tamoxifen-treatment

congestive heart failure ( J:325413 )

• post tamoxifen-treatment

growth/size/body

increased heart weight ( J:325413 )

• post tamoxifen-treatment

cardiac hypertrophy ( J:325413 )

• post tamoxifen-treatment

muscle

increased myocardial fiber size ( J:325413 )

• increased cross-sectional area post tamoxifen-treatment

decreased heart left ventricle muscle contractility ( J:325413 )

• decreased left ventricular function 3 days post tamoxifen-treatment as measured by fractional shortening and left ventricular end-diastolic dimension

abnormal sarcomere morphology ( J:325413 )

• disorganized post tamoxifen-treatment

cellular

dilated mitochondrion ( J:325413 )

• with disrupted calcium regulation in cardiomyocytes post tamoxifen-treatment

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Ppif^tm1Jmol/Ppif^tm1Jmol Slc8b1^{tm1c(EUCOMM)Wtsi}/Slc8b1^{tm1c(EUCOMM)Wtsi}
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6N * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Ppif^tm1Jmol mutation (1 available); any Ppif mutation (18 available)
Slc8b1^{tm1c(EUCOMM)Wtsi} mutation (1 available); any Slc8b1 mutation (45 available)

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

cardiovascular system

cardiac hypertrophy ( J:325413 )

• near complete rescue in tamoxifen-treated mice

decreased heart ventricle muscle contractility ( J:325413 )

• near complete rescue in tamoxifen-treated mice

growth/size/body

cardiac hypertrophy ( J:325413 )

• near complete rescue in tamoxifen-treated mice

muscle

decreased heart ventricle muscle contractility ( J:325413 )

• near complete rescue in tamoxifen-treated mice

abnormal sarcomere morphology ( J:325413 )

• disorganization is nearly completely rescued in tamoxifen-treated mice

Allelic Composition	Cdh2^tm1Glr/Cdh2^{Gt(OST49160)Lex} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S5/SvEvBrd * 129S6/SvEvTac * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Cdh2^{Gt(OST49160)Lex} mutation (1 available); any Cdh2 mutation (51 available)
Cdh2^tm1Glr mutation (1 available); any Cdh2 mutation (51 available)

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

mortality/aging

premature death ( J:98828 )

• mutants die about 2 months after tamoxifen treatment

cardiovascular system

abnormal cardiovascular system morphology ( J:98828 )

abnormal myocardial fiber morphology ( J:98828 )

• after tamoxifen treatment enlarged hyperchromatic myocyte nuclei are seen

• after tamoxifen treatment intercalated disc structures and intercellular space are absent

• after tamoxifen treatment sarcomeres appear distorted and compressed with wider, less dense Z-lines

abnormal intercalated disk morphology ( J:98828 )

• after tamoxifen treatment intercalated disc structures are absent

dilated heart atrium ( J:98828 )

• modest dilation of the atria after tamoxifen treatment

abnormal heart shape ( J:98828 )

• after tamoxifen treatment hearts appear elongated and flacid

dilated heart left ventricle ( J:98828 )

• modest dilation of the ventricles after tamoxifen treatment

dilated heart right ventricle ( J:98828 )

• modest dilation of the ventricles after tamoxifen treatment

abnormal cardiovascular system physiology ( J:98828 )

decreased cardiac output ( J:98828 )

decreased heart left ventricle muscle contractility ( J:98828 )

• left ventricular end-diastolic and end-systolic volume in the cavity are increased and left ventricular ejection fraction is decreased

decreased heart rate ( J:98828 )

• about 5 weeks after tamoxifen treatment, mutant heart rate is significantly reduced

increased heart rate ( J:98828 )

• about 6 weeks after tamoxifen treatment, 2 mutants showed abrupt onset of ventricular tachyarrhythmia followed by sudden death

irregular heartbeat ( J:98828 )

• about 6 weeks after tamoxifen treatment, 2 mutants showed abrupt onset of ventricular tachyarrhythmia followed by sudden death

abnormal impulse conducting system conduction ( J:98828 )

• tachyarrhythmia is initiated by premature ventricular depolarization

muscle

abnormal myocardial fiber morphology ( J:98828 )

• after tamoxifen treatment enlarged hyperchromatic myocyte nuclei are seen

• after tamoxifen treatment intercalated disc structures and intercellular space are absent

• after tamoxifen treatment sarcomeres appear distorted and compressed with wider, less dense Z-lines

abnormal intercalated disk morphology ( J:98828 )

• after tamoxifen treatment intercalated disc structures are absent

decreased heart left ventricle muscle contractility ( J:98828 )

• left ventricular end-diastolic and end-systolic volume in the cavity are increased and left ventricular ejection fraction is decreased

Allelic Composition	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Tgfbr2^tm1.2Hlm mutation (0 available); any Tgfbr2 mutation (40 available)

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

cardiovascular system

cardiovascular system phenotype ( J:164749 )

N	• treatment of mice with oral dose of 160 mg/kg BW per day raloxifene for 21 days resulted in similar recombinase activity as the tamoxifen regimen, but does not cause any cardiac dysfunction; lower (20 mg/kg BW) oral tamoxifen treatment for 21 days does not cause dysfunction

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing significantly

mortality/aging

premature death ( J:164749 )

• by 6 days following IP tamoxifen treatment (80 mg/kg BW for 5 days), 60% mortality of treated mice is observed

muscle

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing significantly

Allelic Composition	Plce1^tm2Avsm/Plce1^tm2Avsm A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Plce1^tm2Avsm mutation (0 available); any Plce1 mutation (111 available)

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

cardiovascular system

decreased response of heart to induced stress ( J:197247 )

• following transverse aortic constriction, mice exhibit diminished cardiac hypertrophy compared with control mice

homeostasis/metabolism

decreased response of heart to induced stress ( J:197247 )

• following transverse aortic constriction, mice exhibit diminished cardiac hypertrophy compared with control mice

Allelic Composition	Jup^tm1.1Glr/Jup^tm1.1Glr A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Jup^tm1.1Glr mutation (1 available); any Jup mutation (160 available)

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

mortality/aging

premature death ( J:170618 )

• increase in cardiac death compared to controls beginning about 3 months after tamoxifen treatment

cardiovascular system

cardiovascular system phenotype ( J:170618 )

N	• unlike in human patients with Arrhythmogenic Right Ventricular Dysplasia replacement of myocytes with adipocytes is not seen in tamoxifen treated mice and tamoxifen treated mice are not more susceptible to induced arrhythmias

abnormal myocardial fiber morphology ( J:170618 )

• decrease in the number and length of desmosomes in tamoxifen treated mice

• adherens-type junctions with less submembranous electron-dense material are prominently seen in tamoxifen treated mice

abnormal intercalated disk morphology ( J:170618 )

• mislocalization of desmosomal proteins to the intercalated disc in tamoxifen treated mice

increased myocardial fiber size ( J:170618 )

• increase in cardiomyocyte cross sectional area with age in tamoxifen treated mice

increased heart weight ( J:170618 )

• increase in the heart to body weight ratio with age in tamoxifen treated mice

increased heart left ventricle size ( J:170618 )

• by about 5 months after tamoxifen treatment

heart left ventricle hypertrophy ( J:170618 )

• mild left ventricle hypertrophy in tamoxifen treated mice

dilated heart left ventricle ( J:170618 )

• modest left ventricle dilation in tamoxifen treated mice

abnormal heart right ventricle morphology ( J:170618 )

• progressive thinning of the right ventricular free wall is seen after tamoxifen treatment

increased heart right ventricle size ( J:170618 )

• by about 5 months after tamoxifen treatment

cardiac fibrosis ( J:170618 )

• focal areas of myocyte loss and replacement with fibrous tissue are seen after tamoxifen treatment

abnormal cardiovascular system physiology ( J:170618 )

• increased apoptosis is seen at 5 months after tamoxifen treatment

• apoptotic cells are associated with fibrotic areas

• heart failure is seen in some tamoxifen treated mice

decreased heart left ventricle muscle contractility ( J:170618 )

• reduction of left ventricular fractional shortening and ejection fraction in tamoxifen treated mice

heart inflammation ( J:170618 )

• infiltration of activated macrophages/monocytes in areas adjacent to apoptotic myocytes in tamoxifen treated mice

• neutrophil infiltrations are also seen in tamoxifen treated mice

muscle

abnormal myocardial fiber morphology ( J:170618 )

• decrease in the number and length of desmosomes in tamoxifen treated mice

• adherens-type junctions with less submembranous electron-dense material are prominently seen in tamoxifen treated mice

abnormal intercalated disk morphology ( J:170618 )

• mislocalization of desmosomal proteins to the intercalated disc in tamoxifen treated mice

increased myocardial fiber size ( J:170618 )

• increase in cardiomyocyte cross sectional area with age in tamoxifen treated mice

heart left ventricle hypertrophy ( J:170618 )

• mild left ventricle hypertrophy in tamoxifen treated mice

decreased heart left ventricle muscle contractility ( J:170618 )

• reduction of left ventricular fractional shortening and ejection fraction in tamoxifen treated mice

abnormal sarcomere morphology ( J:170618 )

• cardiomyocyte sarcomeres appear distorted and compressed in tamoxifen treated mice

• decreased cardiomyocyte sarcomere length in tamoxifen treated mice

diffuse Z line ( J:170618 )

• cardiomyocyte sarcomeres have wider, less dense Z lines in tamoxifen treated mice

homeostasis/metabolism

pulmonary edema ( J:170618 )

• seen at 9 - 12 months after tamoxifen treatment, associated with heart failure

abnormal interleukin level ( J:170618 )

• increase in the IL6 and IL1B levels in heart lysates from tamoxifen treated mice

• increase in cytokine expression is associated with the severity of myocyte loss

immune system

heart inflammation ( J:170618 )

• infiltration of activated macrophages/monocytes in areas adjacent to apoptotic myocytes in tamoxifen treated mice

• neutrophil infiltrations are also seen in tamoxifen treated mice

abnormal interleukin level ( J:170618 )

• increase in the IL6 and IL1B levels in heart lysates from tamoxifen treated mice

• increase in cytokine expression is associated with the severity of myocyte loss

respiratory system

pulmonary edema ( J:170618 )

• seen at 9 - 12 months after tamoxifen treatment, associated with heart failure

growth/size/body

heart left ventricle hypertrophy ( J:170618 )

• mild left ventricle hypertrophy in tamoxifen treated mice

increased heart weight ( J:170618 )

• increase in the heart to body weight ratio with age in tamoxifen treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arrhythmogenic right ventricular dysplasia 12		DOID:0110083	OMIM:611528	J:170618

Allelic Composition	Wdr1^tm1.1Zzy/Wdr1^tm1.1Zzy A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Wdr1^tm1.1Zzy mutation (0 available); any Wdr1 mutation (41 available)

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

mortality/aging

premature death ( J:211364 )

• when treated with tamoxifen at 2 months of age, mice begin to die at 56 days after the first tamoxifen injection, and none survive past 104 days

cardiovascular system

abnormal myocardial fiber morphology ( J:211364 )

• F-actin accumulations are observed within myofibrils at 1 month after the first tamoxifen injection

increased myocardial fiber size ( J:211364 )

• cardiomyocyte size is increased at 1 month after the first tamoxifen injection

increased heart weight ( J:211364 )

• in male mice, the heart weight/body weight ratio begins to increase at 1 month after the first tamoxifen injection

• however, no significant changes are observed in tamoxifen-treated female mice

cardiac hypertrophy ( J:211364 )

• tamoxifen-treated mice exhibit a milder heart hypertrophy relative to that observed in mice that are homozygous for Wdr1^tm1.1Zzy and hemizygous for Tg(Myhc-cre)1Xya

muscle

abnormal myocardial fiber morphology ( J:211364 )

• F-actin accumulations are observed within myofibrils at 1 month after the first tamoxifen injection

increased myocardial fiber size ( J:211364 )

• cardiomyocyte size is increased at 1 month after the first tamoxifen injection

growth/size/body

increased heart weight ( J:211364 )

• in male mice, the heart weight/body weight ratio begins to increase at 1 month after the first tamoxifen injection

• however, no significant changes are observed in tamoxifen-treated female mice

cardiac hypertrophy ( J:211364 )

• tamoxifen-treated mice exhibit a milder heart hypertrophy relative to that observed in mice that are homozygous for Wdr1^tm1.1Zzy and hemizygous for Tg(Myhc-cre)1Xya

Allelic Composition	Cdh2^tm1Glr/Cdh2^tm1Hyn A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Cdh2^tm1Glr mutation (1 available); any Cdh2 mutation (51 available)
Cdh2^tm1Hyn mutation (1 available); any Cdh2 mutation (51 available)

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

mortality/aging

premature death ( J:98828 )

• mutants die about 2 months after tamoxifen treatment

cardiovascular system

abnormal cardiovascular system morphology ( J:98828 )

abnormal myocardial fiber morphology ( J:98828 )

• after tamoxifen treatment enlarged hyperchromatic myocyte nuclei are seen

• after tamoxifen treatment intercalated disc structures and intercellular space are absent

• after tamoxifen treatment sarcomeres appear distorted and compressed with wider, less dense Z-lines

abnormal intercalated disk morphology ( J:98828 )

• after tamoxifen treatment intercalated disc structures are absent

dilated heart atrium ( J:98828 )

• modest dilation of the atria after tamoxifen treatment

abnormal heart shape ( J:98828 )

• after tamoxifen treatment hearts appear elongated and flacid

dilated heart left ventricle ( J:98828 )

• modest dilation of the ventricles after tamoxifen treatment

dilated heart right ventricle ( J:98828 )

• modest dilation of the ventricles after tamoxifen treatment

abnormal cardiovascular system physiology ( J:98828 )

decreased cardiac output ( J:98828 )

decreased heart left ventricle muscle contractility ( J:98828 )

• eft ventricular end-diastolic and end-systolic volume in the cavity are increased and left ventricular ejection fraction is decreased

decreased heart rate ( J:98828 )

• about 5 weeks after tamoxifen treatment, mutant heart rate is significantly reduced

increased heart rate ( J:98828 )

• about 6 weeks after tamoxifen treatment, 2 mutants showed abrupt onset of ventricular tachyarrhythmia followed by sudden death

irregular heartbeat ( J:98828 )

• about 6 weeks after tamoxifen treatment, 2 mutants showed abrupt onset of ventricular tachyarrhythmia followed by sudden death

abnormal impulse conducting system conduction ( J:98828 )

• tachyarrhythmia is initiated by premature ventricular depolarization

muscle

abnormal myocardial fiber morphology ( J:98828 )

• after tamoxifen treatment enlarged hyperchromatic myocyte nuclei are seen

• after tamoxifen treatment intercalated disc structures and intercellular space are absent

• after tamoxifen treatment sarcomeres appear distorted and compressed with wider, less dense Z-lines

abnormal intercalated disk morphology ( J:98828 )

• after tamoxifen treatment intercalated disc structures are absent

decreased heart left ventricle muscle contractility ( J:98828 )

• eft ventricular end-diastolic and end-systolic volume in the cavity are increased and left ventricular ejection fraction is decreased

Allelic Composition	Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S/Sv * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Tgfbr1^tm1.1Karl mutation (1 available); any Tgfbr1 mutation (31 available)

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

mortality/aging

premature death ( J:164749 )

• by 6 days following IP tamoxifen treatment (80 mg/kg BW for 5 days), 60% mortality of treated mice is observed

cardiovascular system

cardiovascular system phenotype ( J:164749 )

N	• treatment of mice with oral dose of 160 mg/kg BW per day raloxifene for 21 days resulted in similar recombinase activity as the tamoxifen regimen, but does not cause any cardiac dysfunction; lower (20 mg/kg BW) oral tamoxifen treatment for 21 days does not cause dysfunction

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing significantly

muscle

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing significantly

Allelic Composition	Hcn4^tm1.1Ggc/Hcn4^tm1.1Ggc A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129S/SvEv * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Hcn4^tm1.1Ggc mutation (0 available); any Hcn4 mutation (65 available)

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

cardiovascular system

decreased heart rate ( J:168248 )

• develop severe bradycardia when injected daily with tamoxifen which leads eventually to death

• heart rate reduced by 32% after 2 days of treatment and by 47% after 6 days

• isolated cells from the sino-atrial node of mice treated with tamoxifen beat spontaneously but more slowly than control cells and become progressively slower as treatment is continued to 5 days

• mice injected with isoproterenol experience heart beat acceleration similar to that occurring in control mice

abnormal impulse conducting system conduction ( J:168248 )

atrioventricular block ( J:168248 )

• when injected daily with tamoxifen, atrioventricular block becomes a 2nd degree block

• conduction ratio progresses from 2:1 to 4:1 or more

prolonged PQ interval ( J:168248 )

• when mice are injected daily with tamoxifen, a prolonged PQ interval is observed

abnormal sinoatrial node conduction ( J:168248 )

• f-channel current densities from atrioventricular cells isolated from mice after 2 and 5 days of treatment with tamoxifen are lower than for control cells

• there is a time dependent decrease in f-channel conductance

mortality/aging

premature death ( J:168248 )

• no mice survive beyond 8.5 days of treatment with tamoxifen

Allelic Composition	Myocd^tm1Msp/Myocd^tm1Msp A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129/Sv * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Myocd^tm1Msp mutation (0 available); any Myocd mutation (55 available)

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

mortality/aging

premature death ( J:154666 )

• 4 month old mice treated with tamoxifen become lethargic within 3-4 days of tamoxifen exposure and die within 7 days

cardiovascular system

abnormal myocardial fiber morphology ( J:154666 )

• derangements in cardiomyocyte structure and myofibrillar organization are seen throughout the hearts of tamoxifen-treated adult mice

• myofibrillar striations are absent in tamoxifen-treated hearts

• cardiomyocytes of tamoxifen-treated adult mice exhibit indistinct desmosomes and adherens junctions

abnormal intercalated disk morphology ( J:154666 )

• structure of the intercalated disc is disrupted in the hearts of tamoxifen-treated adult mice

myocardial fiber degeneration ( J:154666 )

• loss of cardiomyocytes in tamoxifen-treated adults

myocardial fiber disarray ( J:154666 )

• cardiomyocyte disarray with myocyte loss in hearts of tamoxifen-treated adult mice

• sparse, randomly oriented myofibers are seen throughout the sarcoplasm of hearts of tamoxifen-treated adult mice

enlarged heart ( J:154666 )

• hearts of tamoxifen-treated adult mice are enlarged

pericardial effusion ( J:154666 )

• hearts of tamoxifen-treated adult mice show large pericardial effusions

cardiac fibrosis ( J:154666 )

• fibrosis in hearts of tamoxifen-treated adult mice

dilated cardiomyopathy ( J:154666 )

• 6 days after tamoxifen treatment, adult mice exhibit severe dilated cardiomyopathy involving all 4 chambers

decreased cardiac muscle contractility ( J:154666 )

• mean ejection fraction is decreased in tamoxifen-treated adult mice

growth/size/body

enlarged heart ( J:154666 )

• hearts of tamoxifen-treated adult mice are enlarged

cellular

increased cardiomyocyte apoptosis ( J:154666 )

• widespread cardiomyocyte apoptosis in tamoxifen-treated adult mice

homeostasis/metabolism

pericardial effusion ( J:154666 )

• hearts of tamoxifen-treated adult mice show large pericardial effusions

muscle

abnormal myocardial fiber morphology ( J:154666 )

• derangements in cardiomyocyte structure and myofibrillar organization are seen throughout the hearts of tamoxifen-treated adult mice

• myofibrillar striations are absent in tamoxifen-treated hearts

• cardiomyocytes of tamoxifen-treated adult mice exhibit indistinct desmosomes and adherens junctions

abnormal intercalated disk morphology ( J:154666 )

• structure of the intercalated disc is disrupted in the hearts of tamoxifen-treated adult mice

myocardial fiber degeneration ( J:154666 )

• loss of cardiomyocytes in tamoxifen-treated adults

myocardial fiber disarray ( J:154666 )

• cardiomyocyte disarray with myocyte loss in hearts of tamoxifen-treated adult mice

• sparse, randomly oriented myofibers are seen throughout the sarcoplasm of hearts of tamoxifen-treated adult mice

dilated cardiomyopathy ( J:154666 )

• 6 days after tamoxifen treatment, adult mice exhibit severe dilated cardiomyopathy involving all 4 chambers

decreased cardiac muscle contractility ( J:154666 )

• mean ejection fraction is decreased in tamoxifen-treated adult mice

increased cardiomyocyte apoptosis ( J:154666 )

• widespread cardiomyocyte apoptosis in tamoxifen-treated adult mice

abnormal sarcomere morphology ( J:154666 )

• loss of sarcomeres in the hearts of tamoxifen-treated adult mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:154666

Allelic Composition	Ctnna1^tm1Efu/Ctnna1^tm1Efu A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: 129X1/SvJ * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Ctnna1^tm1Efu mutation (1 available); any Ctnna1 mutation (133 available)

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

cardiovascular system

dilated cardiomyopathy ( J:197814 )

• progressive 8 months after tamoxifen treatment

muscle

dilated cardiomyopathy ( J:197814 )

• progressive 8 months after tamoxifen treatment

Allelic Composition	Dmd^tm1.1Know/Dmd^tm1.1Know A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(Myh6-2A)#Know/0
Genetic Background	involves: BALB/c * C3H * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Dmd^tm1.1Know mutation (0 available); any Dmd mutation (162 available)
Tg(Myh6-2A)#Know mutation (0 available)

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

Inhibition of dilated cardiomyopathy in Dmd^tm1.1Know/Dmd^tm1.1Know Tg(Myh6-2A)#Know/0 A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/0 mice

cardiovascular system

cardiac fibrosis ( J:207775 )

• less severe fibrosis in tamoxifen-treated mice

increased cardiac muscle contractility ( J:207775 )

• improved cardiac function in tamoxifen-treated mice

abnormal heart echocardiography feature ( J:207775 )

• improved cardiac function in tamoxifen-treated mice

cardiomyopathy ( J:207775 )

• less severe cardiomyopathy in tamoxifen-treated mice

homeostasis/metabolism

decreased susceptibility to injury ( J:207775 )

• tamoxifen-treated mice exhibit less severe cardiomyopathy, cardiac fibrosis and improved cardiac function compared with control mice

muscle

increased cardiac muscle contractility ( J:207775 )

• improved cardiac function in tamoxifen-treated mice

cardiomyopathy ( J:207775 )

• less severe cardiomyopathy in tamoxifen-treated mice

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(Myh6-2A)#Know/0
Genetic Background	involves: BALB/c * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Tg(Myh6-2A)#Know mutation (0 available)

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

cardiovascular system

abnormal myocardial fiber morphology ( J:128060 )

• cardiac cells from tamoxifen-treated mice show severe cytoskeletal changes such as myofibrillar collapse with a haphazard arrangement, a decrease in myofibril number, and an increase in swollen mitochondria

• irregularity in the spacing between cells in the intercalated discs and irregularity of the sarcolemmal membrane in the hearts of tamoxifen-treated mice

abnormal intercalated disk morphology ( J:128060 )

• myocardial fibers of tamoxifen-treated mice show abnormalities of intercalated discs

increased heart atrium size ( J:128060 )

• biatrial enlargement in tamoxifen-treated mice

increased heart ventricle size ( J:128060 )

• severe ventricular enlargement in tamoxifen-treated mice

cardiac interstitial fibrosis ( J:128060 )

• small amount of interstitial fibrosis in tamoxifen-treated mice

dilated cardiomyopathy ( J:128060 )

• heart weight-to-body weight ratio is increased 22 days after tamoxifen administration

decreased heart left ventricle muscle contractility ( J:128060 )

• decrease in the fractional shortening of the left ventricle of tamoxifen-treated mice

abnormal heart echocardiography feature ( J:128060 )

• increase in left ventricular end-diastolic dimension and end-systolic dimension in tamoxifen-treated mice

heart inflammation ( J:128060 )

• tamoxifen-treated mice show only a small increase in inflammation

homeostasis/metabolism

ascites ( J:128060 )

• in tamoxifen-treated mice

pleural effusion ( J:128060 )

• in tamoxifen-treated mice

immune system

heart inflammation ( J:128060 )

• tamoxifen-treated mice show only a small increase in inflammation

muscle

abnormal myocardial fiber morphology ( J:128060 )

• irregularity in the spacing between cells in the intercalated discs and irregularity of the sarcolemmal membrane in the hearts of tamoxifen-treated mice

abnormal intercalated disk morphology ( J:128060 )

• myocardial fibers of tamoxifen-treated mice show abnormalities of intercalated discs

dilated cardiomyopathy ( J:128060 )

• heart weight-to-body weight ratio is increased 22 days after tamoxifen administration

decreased heart left ventricle muscle contractility ( J:128060 )

• decrease in the fractional shortening of the left ventricle of tamoxifen-treated mice

abnormal sarcolemma morphology ( J:128060 )

• the sarcolemmal membrane is disrupted in myocardial fibers of tamoxifen-treated mice

abnormal sarcomere morphology ( J:128060 )

• myocardial fibers from tamoxifen-treated mice show shortened sarcomeres

abnormal Z line morphology ( J:128060 )

• myocardial fibers from tamoxifen-treated mice show fuzzy Z-lines

respiratory system

pleural effusion ( J:128060 )

• in tamoxifen-treated mice

cellular

cardiac interstitial fibrosis ( J:128060 )

• small amount of interstitial fibrosis in tamoxifen-treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:128060

Allelic Composition	Hspd1^{tm1c(EUCOMM)Hmgu}/Hspd1^{tm1c(EUCOMM)Hmgu} A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: Black Swiss * C57BL/6 * C57BL/6N * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Hspd1^{tm1c(EUCOMM)Hmgu} mutation (0 available); any Hspd1 mutation (45 available)

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

mortality/aging

premature death ( J:283049 )

• all mice die within 14 weeks post tamoxifen injection

cardiovascular system

enlarged heart ( J:283049 )

• mice show enlarged hearts 11 weeks post tamoxifen injection

abnormal heart ventricles weight ( J:283049 )

• ratio of ventricular weight to body weight is increased at 11 weeks post tamoxifen injection

thin ventricular wall ( J:283049 )

• ventricular wall thinning is seen at 11 weeks post tamoxifen injection

dilated heart ventricle ( J:283049 )

• ventricular chamber dilation is seen at 11 weeks post tamoxifen injection

cardiac fibrosis ( J:283049 )

• hearts show severe cardiac fibrosis at 11 weeks post tamoxifen injection

abnormal cardiovascular system physiology ( J:283049 )

• increase in number of apoptotic cells is seen in hearts at 11 weeks post tamoxifen injection

dilated cardiomyopathy ( J:283049 )

• mice develop dilated cardiomyopathy after tamoxifen injection

decreased heart left ventricle muscle contractility ( J:283049 )

• left ventricle fractional shortening and ejection fraction are slightly decreased at 9 weeks and further decreased at 11 and 13 weeks after tamoxifen injection

abnormal heart echocardiography feature ( J:283049 )

• left ventricle systolic function represented by fractional shortening and ejection fraction is slightly decreased at 9 weeks post tamoxifen injection and further increased at 11 and 13 weeks after tamoxifen injection

• enlarged left ventricle chamber and ventricular wall thinning are seen at 11 and 13 weeks after tamoxifen injection

• left ventricle systolic function further deteriorates at 11 and 13 weeks after tamoxifen injection

• however, ventricular wall thickness and internal dimension of the heart are not altered at 9 weeks post tamoxifen injection

congestive heart failure ( J:283049 )

• mice develop dilated cardiomyopathy and heart failure after tamoxifen injection

cellular

abnormal mitochondrial physiology ( J:283049 )

• activities of complex I and complex III in mitochondria are impaired at 9 weeks post tamoxifen injection

• activities of all four complexes in mitochondria are impaired at 11 weeks post tamoxifen injection

• cardiomyocytes show reduced mitochondrial potential and increased mitochondrial ROS levels at 9 weeks post tamoxifen injection

oxidative stress ( J:283049 )

• cardiomyocytes show increased mitochondrial ROS levels at 9 weeks post tamoxifen injection

muscle

dilated cardiomyopathy ( J:283049 )

• mice develop dilated cardiomyopathy after tamoxifen injection

decreased heart left ventricle muscle contractility ( J:283049 )

• left ventricle fractional shortening and ejection fraction are slightly decreased at 9 weeks and further decreased at 11 and 13 weeks after tamoxifen injection

respiratory system

increased lung weight ( J:283049 )

• ratio of lung weight to body weight are increased at 11 weeks post tamoxifen injection

growth/size/body

enlarged heart ( J:283049 )

• mice show enlarged hearts 11 weeks post tamoxifen injection

increased lung weight ( J:283049 )

• ratio of lung weight to body weight are increased at 11 weeks post tamoxifen injection

Allelic Composition	Tspo^tm1.1Maf/Tspo^tm1.1Maf A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Tspo^tm1.1Maf mutation (1 available); any Tspo mutation (16 available)

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

cardiovascular system

cardiovascular system phenotype ( J:214129 )

N	• tamoxifen treated mice show a similiar response to ischemia/reperfusion injury as controls

Allelic Composition	Tnni3k^tm1Tfo/Tnni3k^tm1Tfo A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Tnni3k^tm1Tfo mutation (0 available); any Tnni3k mutation (47 available)

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

cardiovascular system

cardiovascular system phenotype ( J:213546 )

N	• tamoxifen-treated mice exhibit normal left ventricle function and cardiac morphometry and normal left ventricular remodeling after permanent occlusion myoinfarction

abnormal myocardial fiber physiology ( J:213546 )

• decreased cell death in tamoxifen-treated mice following ischemic injury

abnormal response to cardiac infarction ( J:213546 )

• following ischemic/reperfusion injury, tamoxifen-treated mice exhibit decreased infarct size and cardiomyocyte cell death compared with wild-type mice

• however, normal left ventricular remodeling after permanent occlusion myoinfarction

decreased myocardial infarct size ( J:213546 )

• in tamoxifen-treated mice following ischemic/reperfusion injury

homeostasis/metabolism

abnormal response to cardiac infarction ( J:213546 )

• following ischemic/reperfusion injury, tamoxifen-treated mice exhibit decreased infarct size and cardiomyocyte cell death compared with wild-type mice

• however, normal left ventricular remodeling after permanent occlusion myoinfarction

decreased myocardial infarct size ( J:213546 )

• in tamoxifen-treated mice following ischemic/reperfusion injury

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Pakap^tm1.1Div/Pakap^tm1.1Div
Genetic Background	involves: C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Pakap^tm1.1Div mutation (0 available); any Pakap mutation (4 available)

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

cardiovascular system

increased response of heart to induced stress ( J:345193 )

• in tamoxifen treated mice ligation of the left anterior descending coronary artery induces increased thinning of the left ventricular posterior wall and intraventricular septum and increased ventricular dilation

• in tamoxifen treated mice ligation of the left anterior descending coronary artery induces more severe cardiac dysfunction as indicated by significantly reduced fractional shortening and ejection fraction

• however, hearts of tamoxifen treated mice do not show abnormalities prior to ligation of the left anterior descending coronary artery

abnormal response to cardiac infarction ( J:345193 )

• in tamoxifen treated mice at 2 weeks post cardiac infarction left ventricular vessel density is reduced in the infarcted zone and border zone compared to controls

increased susceptibility to myocardial ischemic injury ( J:345193 )

• increased apoptosis in hearts of tamoxifen treated mice at 24 hours after ligation of the left anterior descending coronary artery

increased myocardial infarct size ( J:345193 )

• in tamoxifen treated mice increased infarct size at 2 weeks after ligation of the left anterior descending coronary artery

homeostasis/metabolism

increased response of heart to induced stress ( J:345193 )

• however, hearts of tamoxifen treated mice do not show abnormalities prior to ligation of the left anterior descending coronary artery

abnormal response to cardiac infarction ( J:345193 )

• in tamoxifen treated mice at 2 weeks post cardiac infarction left ventricular vessel density is reduced in the infarcted zone and border zone compared to controls

increased susceptibility to myocardial ischemic injury ( J:345193 )

• increased apoptosis in hearts of tamoxifen treated mice at 24 hours after ligation of the left anterior descending coronary artery

increased myocardial infarct size ( J:345193 )

• in tamoxifen treated mice increased infarct size at 2 weeks after ligation of the left anterior descending coronary artery

Allelic Composition	Akap6^tm1.1Mskf/Akap6^tm1.1Mskf A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Akap6^tm1.1Mskf mutation (1 available); any Akap6 mutation (112 available)

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

cardiovascular system

increased myocardial fiber size ( J:214288 )

• following 2 weeks of TAC or isoproterenol infusion, left venticle (LV) myocytes from mice administered tamoxifen exhibit an increase in cross section area, but to a much lessor extent than controls subjected to the same regime

heart left ventricle hypertrophy ( J:214288 )

• following a long term (LT) TAC, mice administered tamoxifen die as a result of congenital heart failure, but exhibit greater survival than controls subjected to the same regime (6% vs 29%) and do not exhibit pulmonary edema

increased heart left atrium weight ( J:214288 )

• following cardiac stress by long term transverse aortic constriction (LT-TAC), mice administered tamoxifen exhibit increased left atrial weight (35%) as compared controls undergoing a sham procedure, but less than the increase (50%) in controls subjected to the same regime

increased heart left ventricle weight ( J:214288 )

• following a LT-TAC, mice administered tamoxifen die as a result of congenital heart failure, but exhibit greater survival than controls subjected to the same regime (6% vs 29%) and do not exhibit pulmonary edema

increased heart left ventricle wall thickness ( J:214288 )

• following 2 weeks of TAC or isoproterenol infusion, mice administered tamoxifen exhibit increased left ventricular (LV) wall thickness, but to a much lessor extent than controls subjected to the same regime

abnormal heart ventricles weight ( J:214288 )

• following 2 weeks of cardiac stress by transverse aortic constriction (TAC) or isoproterenol infusion, mice administered tamoxifen exhibit increased biventricular weight, but to a much lessor extent than controls subjected to the same regime

• following a 5 week swimming regime, mice administered tamoxifen exhibit an increase in biventricular weight gain, but to a lessor extent than controls subjected to the same regime (13% vs 5%)

cardiac interstitial fibrosis ( J:214288 )

• following a long term LT-TAC, mice administered tamoxifen exhibit increased collagen deposistion, but 78% less collagen deposition as compared controls subjected to the same regime

decreased heart rate ( J:214288 )

• following a 5 week swimming regime, mice administered tamoxifen exhibit lower heart rate than controls subjected to the same regime

growth/size/body

heart left ventricle hypertrophy ( J:214288 )

cellular

cardiac interstitial fibrosis ( J:214288 )

• following a long term LT-TAC, mice administered tamoxifen exhibit increased collagen deposistion, but 78% less collagen deposition as compared controls subjected to the same regime

increased cardiomyocyte apoptosis ( J:214288 )

• following a long term LT-TAC, mice administered tamoxifen exhibit increased apoptosis, but 75% less myocardial apoptosis as compared controls subjected to the same regime

muscle

increased myocardial fiber size ( J:214288 )

heart left ventricle hypertrophy ( J:214288 )

increased cardiomyocyte apoptosis ( J:214288 )

• following a long term LT-TAC, mice administered tamoxifen exhibit increased apoptosis, but 75% less myocardial apoptosis as compared controls subjected to the same regime

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(CAG-cat,-Tcf25)1Xdgz/0
Genetic Background	involves: C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Tg(CAG-cat,-Tcf25)1Xdgz mutation (0 available)

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

cardiovascular system

decreased response of heart to induced stress ( J:317382 )

• cardiac hypertrophy induced by aortic banding is blunted with a smaller increase in heart weight , improved cardiac performance, less pronounced hypertrophic morphological changes, and reduced myocardial fibrosis

homeostasis/metabolism

decreased response of heart to induced stress ( J:317382 )

Allelic Composition	Ppp1r12b^em1Chana/Ppp1r12b^em1Chana A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
Genetic Background	involves: C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
A1cf^{Tg(Myh6-cre/Esr1*)1Jmk} mutation (5 available); any A1cf mutation (37 available)
Ppp1r12b^em1Chana mutation (0 available); any Ppp1r12b mutation (75 available)

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

cardiovascular system

cardiovascular system phenotype ( J:346986 )

N	• despite the increase in cardiac myosin regulatory light chain phosphorylation after tamoxifen treatment, no difference in heart size is detected

abnormal myocardial fiber morphology ( J:346986 )

• in tamoxifen treated mice the ratio of myosin in the SRX state to that in the DRX state is shifted with less in the SRX state compared to controls

decreased response of heart to induced stress ( J:346986 )

• tamoxifen treated mice show no cardiac hypertrophy in response to transaortic constriction induced pressure overload

• however, changes on protein expression induced by pressure overload in tamoxifen treated mice are similar to controls

muscle

abnormal myocardial fiber morphology ( J:346986 )

• in tamoxifen treated mice the ratio of myosin in the SRX state to that in the DRX state is shifted with less in the SRX state compared to controls

homeostasis/metabolism

decreased response of heart to induced stress ( J:346986 )

• tamoxifen treated mice show no cardiac hypertrophy in response to transaortic constriction induced pressure overload

• however, changes on protein expression induced by pressure overload in tamoxifen treated mice are similar to controls

Allelic Composition	A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺ Tg(CAG-cat,-Dusp14)4Lyg/0
Genetic Background	involves: C57BL/6J * FVB/N

Find Mice

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

cardiovascular system

increased myocardial fiber size ( J:263251 )