Phenotypes Associated with This Genotype

Genotype
MGI:5906002

• 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

• ♀: 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