Phenotypes Associated with This Genotype

Genotype
MGI:3639520

• Allelic Composition: Tg(Myh6-Acsl1)O7Jesc/0
• Genetic Background: FVB/N-Tg(Myh6-Acsl1)O7Jesc

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

growth/size/body

enlarged heart ( J:68639 )

• at the time of death, heart weight relative to body weight is increased; degree of cardiomegaly is more than in transgenic lines J3 and M13

cardiac hypertrophy ( J:68639 )

• exhibit a 54% increase in cell size in ventricular tissue

heart left ventricle hypertrophy ( J:68639 )

• increase in left ventricular mass developing at 3 weeks of age and progressively increasing over time; develop concentric left-ventricular hypertrophy with preserved systolic function at an early age (3 weeks), followed by a transition to eccentric hypertrophy and marked reduction of systolic function

mortality/aging

premature death ( J:68639 )

• display significant morbidity and mortality; all die by 100 days of age of heart failure

homeostasis/metabolism

cyanosis ( J:68639 )

• develops as early as 4 weeks of age

abnormal lipid level ( J:68639 )

• exhibit lipid accumulation in cardiac myocytes

increased cardiac muscle triglyceride level ( J:68639 )

• display a 12-fold increase in triglyceride content with broad acyl-chain dristribution (C14 to C18), including both saturated and unsaturated species, in the heart

abnormal phospholipid level ( J:68639 )

• observe a 50% increase in choline glycerophospholipids and a 15% increase in ethanolamine glycerophospholipids in the heart

• for both choline and ethanolamine glycerophospholipids there is a shift in fatty acid composition at the SN-2 position, with increases in 18:1, 18:2, and 20:4 species and decreases in 20:6

cardiovascular system

increased cardiac muscle triglyceride level ( J:68639 )

• display a 12-fold increase in triglyceride content with broad acyl-chain dristribution (C14 to C18), including both saturated and unsaturated species, in the heart

abnormal myocardial fiber morphology ( J:68639 )

• exhibit lipid accumulation in cardiac myocytes

enlarged heart ( J:68639 )

• at the time of death, heart weight relative to body weight is increased; degree of cardiomegaly is more than in transgenic lines J3 and M13

cardiac hypertrophy ( J:68639 )

• exhibit a 54% increase in cell size in ventricular tissue

heart left ventricle hypertrophy ( J:68639 )

• increase in left ventricular mass developing at 3 weeks of age and progressively increasing over time; develop concentric left-ventricular hypertrophy with preserved systolic function at an early age (3 weeks), followed by a transition to eccentric hypertrophy and marked reduction of systolic function

thick ventricular wall ( J:68639 )

• wall thickness is increased at 3 weeks of age but subsequently decreased below controls

cardiac interstitial fibrosis ( J:68639 )

• seen in 28-week old mutants

abnormal cardiovascular system physiology ( J:68639 )

decreased ventricle muscle contractility ( J:68639 )

• exhibit normal fractional shortening at 2 and 3 weeks of age but marked deterioration of systolic performance from 4 weeks onward

decreased left ventricle systolic pressure ( J:68639 )

• seen from 4 weeks of age onward

increased cardiomyocyte apoptosis ( J:68639 )

• exhibit an increase in TUNEL-positive cells, significant cytochrome c release from mitochondria, and a 3.3-fold increase in total cardiac ceramide content, indicating increased apoptosis

cardiomyopathy ( J:68639 )

• develop metabolic/lipotoxic cardiomyopathy

congestive heart failure ( J:68639 )

• develop heart failure as early as 4 weeks of age

behavior/neurological

lethargy ( J:68639 )

• develops as early as 4 weeks of age

muscle

increased cardiac muscle triglyceride level ( J:68639 )

• display a 12-fold increase in triglyceride content with broad acyl-chain dristribution (C14 to C18), including both saturated and unsaturated species, in the heart

abnormal myocardial fiber morphology ( J:68639 )

• exhibit lipid accumulation in cardiac myocytes

heart left ventricle hypertrophy ( J:68639 )

• increase in left ventricular mass developing at 3 weeks of age and progressively increasing over time; develop concentric left-ventricular hypertrophy with preserved systolic function at an early age (3 weeks), followed by a transition to eccentric hypertrophy and marked reduction of systolic function

decreased ventricle muscle contractility ( J:68639 )

• exhibit normal fractional shortening at 2 and 3 weeks of age but marked deterioration of systolic performance from 4 weeks onward

increased cardiomyocyte apoptosis ( J:68639 )

• exhibit an increase in TUNEL-positive cells, significant cytochrome c release from mitochondria, and a 3.3-fold increase in total cardiac ceramide content, indicating increased apoptosis

cardiomyopathy ( J:68639 )

• develop metabolic/lipotoxic cardiomyopathy

respiratory system

abnormal breathing pattern ( J:68639 )

• develop shortness of breath as early as 4 weeks of age

cellular

cardiac interstitial fibrosis ( J:68639 )

• seen in 28-week old mutants

increased cardiomyocyte apoptosis ( J:68639 )

• exhibit an increase in TUNEL-positive cells, significant cytochrome c release from mitochondria, and a 3.3-fold increase in total cardiac ceramide content, indicating increased apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:68639