Phenotypes Associated with This Genotype

Genotype
MGI:5805256

• Allelic Composition: Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB/N

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

mortality/aging

premature death ( J:229455 )

• median lifespan of 46 weeks

cardiovascular system

cardiac muscle necrosis ( J:229455 )

• ongoing cardiomyocyte necrotic cell death

abnormal heart morphology ( J:229455 )

• hearts show increased endogenous glucose levels and decreased lactate levels

• however, levels of citric acid cycle intermediates are not altered

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

dilated heart left ventricle ( J:229455 )

• dilated left ventricular chamber

• however, left ventricular mass is preserved

cardiac fibrosis ( J:229455 )

• myocardial fibrosis

abnormal cardiovascular system physiology ( J:229455 )

• progressive heart dysfunction which becomes apparent at 20 weeks

• mice fed a high-fat diet beginning at 9 weeks of age show normal cardiac glucose uptake, normal levels of endogenous cardiac glucose and acylcarnitine, restoration of cardiac function, prevention of cardiac fibrosis, normal exercise tolerance and left ventricular ejection fraction, suppressed heart failure and restored life span

dilated cardiomyopathy ( J:229455 )

• dilated cardiomyopathy progresses to heart failure in middle age

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased ventricle muscle contractility ( J:229455 )

• reduction in percentage of left ventricular ejection fraction

congestive heart failure ( J:229455 )

growth/size/body

weight loss ( J:229455 )

• weight loss before death

homeostasis/metabolism

increased circulating troponin T level ( J:229455 )

• increase in serum cardiac troponin T levels

cellular

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

cardiac muscle necrosis ( J:229455 )

• ongoing cardiomyocyte necrotic cell death

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased mitochondrial size ( J:229455 )

• smaller mitochondria with normal cristae architecture in hearts

abnormal mitochondrial physiology ( J:229455 )

• specific activities of mitochondrial complexes II, III, and IV are increased in cardiomyocytes

• only moderately impaired ATP synthesis by complex V in hearts

muscle

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

cardiac muscle necrosis ( J:229455 )

• ongoing cardiomyocyte necrotic cell death

abnormal muscle physiology ( J:229455 )

• in vitro cardiomyocyte glycolysis rates are increased

• global reduction of total cardiac acylcarnitines, indicating reduced beta oxidation in cardiomyocytes

dilated cardiomyopathy ( J:229455 )

• dilated cardiomyopathy progresses to heart failure in middle age

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased ventricle muscle contractility ( J:229455 )

• reduction in percentage of left ventricular ejection fraction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:229455