Phenotypes Associated with This Genotype

Genotype
MGI:7523000

• Allelic Composition: Rtf1^{tm1c(KOMP)Wtsi}/Rtf1^{tm1c(KOMP)Wtsi}; A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
• Genetic Background: involves: C57BL/6N * FVB/N

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

mortality/aging

premature death ( J:338311 )

• mice do not survive longer than 3 weeks after knockout initiation by tamoxifen (TAM) feeding

cardiovascular system

abnormal intercalated disk morphology ( J:338311 )

• after 3 weeks of TAM feeding, heart left ventricles (LVs) display disrupted intercalated discs with markedly reduced junctional proteins

• LVs exhibit patchy, weak N-cadherin (adherens junctions/area composita) and Connexin-43 (gap junctions) signals, suggesting altered cell-cell junctions

myocardial fiber disarray ( J:338311 )

• after 3 weeks of TAM feeding, heart LVs exhibit more disorganized myofibrils than control LVs

• however, LVs display parallel lines of alpha-actinin staining, indicating that Z-lines of sarcomeres are intact

thin ventricular wall ( J:338311 )

• after 3 weeks of TAM feeding, hearts display thinning of the ventricular walls

decreased heart left ventricle wall thickness ( J:338311 )

• after 3 weeks of TAM feeding

decreased heart right ventricle wall thickness ( J:338311 )

• after 3 weeks of TAM feeding

dilated heart ventricle ( J:338311 )

• after 3 weeks of TAM feeding, hearts display pronounced dilation of the left (LV) and right (RV) ventricle chambers

dilated heart left ventricle ( J:338311 )

• after 3 weeks of TAM feeding

dilated heart right ventricle ( J:338311 )

• after 3 weeks of TAM feeding

cardiac fibrosis ( J:338311 )

• after 3 weeks of TAM feeding, the LV myocardium is fibrotic with large inclusions of collagen protein in cardiomyocyte-free regions

dilated cardiomyopathy ( J:338311 )

• TAM-fed mice develop progressive left ventricular systolic dysfunction culminating in dilated cardiomyopathy and heart failure

• failing hearts exhibit gene expression changes similar to those observed in human dilated cardiomyopathy

decreased heart ventricle muscle contractility ( J:338311 )

• after 3 weeks of TAM feeding, all hearts are dilated, esp. at systole, and show severely decreased ventricular contractility with 6% FS (fractional shortening) versus 29% FS in controls

decreased heart left ventricle muscle contractility ( J:338311 )

• after 2 weeks of TAM feeding, hearts show a trend of reduced left ventricular function and marked dilation, reflecting compromised contractility

abnormal heart echocardiography feature ( J:338311 )

• after 3 weeks of TAM feeding, ejection fraction (EF) and fractional shortening (FS) values are significantly decreased while values of LV volume at diastole and at systole are markedly increased

• however, LV contractile parameters are normal prior to TAM feeding as well as during the first week of TAM feeding

congestive heart failure ( J:338311 )

• after 3 weeks of TAM feeding, mice exhibit heart failure characterized by disrupted myofibril organization, defective intercalated disc structure, and widespread fibrosis

muscle

abnormal intercalated disk morphology ( J:338311 )

• after 3 weeks of TAM feeding, heart left ventricles (LVs) display disrupted intercalated discs with markedly reduced junctional proteins

• LVs exhibit patchy, weak N-cadherin (adherens junctions/area composita) and Connexin-43 (gap junctions) signals, suggesting altered cell-cell junctions

myocardial fiber disarray ( J:338311 )

• after 3 weeks of TAM feeding, heart LVs exhibit more disorganized myofibrils than control LVs

• however, LVs display parallel lines of alpha-actinin staining, indicating that Z-lines of sarcomeres are intact

dilated cardiomyopathy ( J:338311 )

• TAM-fed mice develop progressive left ventricular systolic dysfunction culminating in dilated cardiomyopathy and heart failure

• failing hearts exhibit gene expression changes similar to those observed in human dilated cardiomyopathy

decreased heart ventricle muscle contractility ( J:338311 )

• after 3 weeks of TAM feeding, all hearts are dilated, esp. at systole, and show severely decreased ventricular contractility with 6% FS (fractional shortening) versus 29% FS in controls

decreased heart left ventricle muscle contractility ( J:338311 )

• after 2 weeks of TAM feeding, hearts show a trend of reduced left ventricular function and marked dilation, reflecting compromised contractility

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:338311