Phenotypes Associated with This Genotype

Genotype
MGI:5575856

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

• ♀: 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 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 )

• 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

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 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 )

• 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 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