Phenotypes Associated with This Genotype

Genotype
MGI:5906203

• Allelic Composition: Ptpn11^tm1Gsf/Ptpn11^tm1Gsf; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

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

growth/size/body

enlarged heart ( J:144767 )

♂ • 66% increase in heart/body weight ratios

mortality/aging

premature death ( J:144767 )

• mice begin to die within 2 weeks after birth and have a median survival age of 13.4 weeks, with very few living up to 36 weeks

cardiovascular system

increased cardiac muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in the heart

• however, no differences in glycogen content of cardiac muscle

increased myocardial fiber size ( J:144767 )

♂ • cardiomyocyte capacitance, a measure of cell size, is augmented, with cells showing a 2-fold increase in capacitance

enlarged heart ( J:144767 )

♂ • 66% increase in heart/body weight ratios

increased heart ventricle size ( J:144767 )

♂

dilated cardiomyopathy ( J:144767 )

♂ • enlarged right and left ventricle chambers with thinner walls

♂ • however, fibrosis, changes in apoptosis or proliferation,or lymphocyte and macrophage infiltration in the heart are not seen

decreased cardiac muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in cardiac muscle cells

decreased heart left ventricle muscle contractility ( J:144767 )

♂ • decrease in left ventricular fraction shortening and the velocity of circumferential fiber shortening

abnormal heart echocardiography feature ( J:144767 )

♂ • enlarged left ventricular chamber size in 6 week old mice, increase in left ventricular internal dimension at end diastole and end systole, and significant wall thinning as evidenced by decrease in systolic dimensions in interventricular septal wall thickness

♂ • however, no change in left ventricular posterior wall thickness is seen

abnormal myocardial fiber calcium currents ( J:144767 )

♂ • cardiomyocytes exhibit slower calcium current density (inward current amplitude normalized to cell capacitance)

congestive heart failure ( J:144767 )

♂

cellular

decreased cardiac muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in cardiac muscle cells

decreased skeletal muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in skeletal muscle cells

homeostasis/metabolism

increased cardiac muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in the heart

• however, no differences in glycogen content of cardiac muscle

increased circulating insulin level ( J:144767 )

♂ • circulating insulin levels under fed and fasted conditions are slightly increased

increased circulating triglyceride level ( J:144767 )

• elevation in levels of triglyceride in plasma

• however, no differences in circulating free fatty acids

impaired glucose tolerance ( J:144767 )

• glucose intolerance, with the most significant difference seen at 120 min after glucose injection

insulin resistance ( J:144767 )

• males and females show a decreased ability to lower circulating glucose levels after intraperitoneal injection of insulin

increased skeletal muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in skeletal muscle

• however, no differences in glycogen content of skeletal muscle

muscle

increased cardiac muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in the heart

• however, no differences in glycogen content of cardiac muscle

increased myocardial fiber size ( J:144767 )

♂ • cardiomyocyte capacitance, a measure of cell size, is augmented, with cells showing a 2-fold increase in capacitance

dilated cardiomyopathy ( J:144767 )

♂ • enlarged right and left ventricle chambers with thinner walls

♂ • however, fibrosis, changes in apoptosis or proliferation,or lymphocyte and macrophage infiltration in the heart are not seen

decreased cardiac muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in cardiac muscle cells

decreased heart left ventricle muscle contractility ( J:144767 )

♂ • decrease in left ventricular fraction shortening and the velocity of circumferential fiber shortening

decreased skeletal muscle cell glucose uptake ( J:144767 )

♂ • glucose uptake is impaired in skeletal muscle cells

increased skeletal muscle triglyceride level ( J:144767 )

• elevation in levels of triglyceride in skeletal muscle

• however, no differences in glycogen content of skeletal muscle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:144767
disease of metabolism		DOID:0014667		J:144767