Phenotypes Associated with This Genotype

Genotype
MGI:5639083

• Allelic Composition: Ptpn11^tm1.1Ics/Ptpn11⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB/N

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

adipose tissue

decreased brown adipose tissue amount ( J:216593 )

• brown adipose tissue is smaller

decreased subcutaneous adipose tissue amount ( J:216593 )

• subcutaneous white adipose tissues are smaller

decreased total body fat amount ( J:216593 )

• fat mass is decreased, showing on average 2/3 less fat mass than wild-type mice

• epididymal, subcutaneous, and perirenal white adipose tissues are smaller

abnormal fat cell differentiation ( J:216593 )

• preadipocytes show impaired differentiation into adipocytes in culture

decreased white fat cell number ( J:216593 )

• adipocyte number is reduced by about half in epididymal fat pads

increased fat cell size ( J:216593 )

• mean diameter is increased in adipocytes of epididymal fat pads and there is a depletion of the small adipocyte subpopulation

• increase in proportion of larger adipocytes in subcutaneous adipose tissue

abnormal epididymal fat pad morphology ( J:216593 )

• epididymal adipose tissues are smaller

increased adipocyte glucose uptake ( J:216593 )

• insulin-induced glucose uptake is increased in isolated adipocytes from epididymal tissue

cardiovascular system

abnormal heart septum morphology ( J:216593 )

• thinning of the intraventricular septum

enlarged heart ( J:216593 )

• increase in heart/body ratio in 30 week old mice

cardiac hypertrophy ( J:216593 )

• mice develop hypertrophic cardiomyopathy that evolves to dilated cardiomyopathy

heart left ventricle hypertrophy ( J:216593 )

• 15 week old mice show enlargement of the left ventricle, showing early stage of hypertrophy

decreased heart left ventricle posterior wall thickness ( J:216593 )

• thinning of the left ventricular posterior wall

dilated heart left ventricle ( J:216593 )

• increase in left ventricular internal diameter

dilated cardiomyopathy ( J:216593 )

decreased cardiac stroke volume ( J:216593 )

decreased cardiac muscle contractility ( J:216593 )

• hearts exhibit cardiac dysfunction as indicated by reduced stroke volume and proportional decrease in fractional shortening and ejection fraction

decreased heart rate ( J:216593 )

• decrease in pulse height and heart rate

decreased systemic arterial blood pressure ( J:216593 )

craniofacial

abnormal cranium size ( J:216593 )

• increase in skull width-to-length ratio

decreased cranium length ( J:216593 )

growth/size/body

enlarged heart ( J:216593 )

• increase in heart/body ratio in 30 week old mice

cardiac hypertrophy ( J:216593 )

• mice develop hypertrophic cardiomyopathy that evolves to dilated cardiomyopathy

heart left ventricle hypertrophy ( J:216593 )

• 15 week old mice show enlargement of the left ventricle, showing early stage of hypertrophy

increased lean body mass ( J:216593 )

• lean mass proportion is increased

decreased susceptibility to diet-induced obesity ( J:216593 )

• mice are resistant to high-fat diet induced obesity, gaining less weight, showing a reduction in fat mass, smaller adipose tissue deposits, lower amount of small adipocytes and more big adipocytes, lower plasma leptin levels, lower glycaemia, reduced insulin levels, a decrease in insulin resistance, improved insulin tolerance, lower cholesterol in plasma, reduction in lipid deposits in the liver and muscle, and lower hepatic triglyceride levels

postnatal growth retardation ( J:216593 )

• slight growth and weight retardation

slow postnatal weight gain ( J:216593 )

• mice gain less weight than wild-type littermates (16% less at 26 weeks of age) despite similar food intake

• chronic treatment with the MEK inhibitor PD0325901, but not rapamycin, results in weight and adiposity gain

enlarged spleen ( J:216593 )

hematopoietic system

enlarged spleen ( J:216593 )

immune system

enlarged spleen ( J:216593 )

muscle

heart left ventricle hypertrophy ( J:216593 )

• 15 week old mice show enlargement of the left ventricle, showing early stage of hypertrophy

dilated cardiomyopathy ( J:216593 )

decreased cardiac muscle contractility ( J:216593 )

• hearts exhibit cardiac dysfunction as indicated by reduced stroke volume and proportional decrease in fractional shortening and ejection fraction

decreased skeletal muscle triglyceride level ( J:216593 )

• in the gastrocnemius muscle

skeleton

abnormal cranium size ( J:216593 )

• increase in skull width-to-length ratio

decreased cranium length ( J:216593 )

vision/eye

ocular hypertelorism ( J:216593 )

• increase in interorbital distance

cellular

abnormal fat cell differentiation ( J:216593 )

• preadipocytes show impaired differentiation into adipocytes in culture

increased adipocyte glucose uptake ( J:216593 )

• insulin-induced glucose uptake is increased in isolated adipocytes from epididymal tissue

homeostasis/metabolism

decreased circulating glucose level ( J:216593 )

• on both a normal diet and high-fat diet

decreased circulating insulin level ( J:216593 )

• on both a normal diet and high-fat diet

decreased circulating leptin level ( J:216593 )

• leptinemia is more than 4-fold reduced

decreased circulating alanine transaminase level ( J:216593 )

increased energy expenditure ( J:216593 )

• mice exhibit enhanced energy expenditure at the whole body level, both under normal diet and high-fat diet

• however, food intake is normal, feces contain similar amounts of energy as wild-type feces, indicating normal intestinal absorption, body temperature is normal, and mice show normal locomotor activity and respiratory quotient

decreased susceptibility to diet-induced obesity ( J:216593 )

• mice are resistant to high-fat diet induced obesity, gaining less weight, showing a reduction in fat mass, smaller adipose tissue deposits, lower amount of small adipocytes and more big adipocytes, lower plasma leptin levels, lower glycaemia, reduced insulin levels, a decrease in insulin resistance, improved insulin tolerance, lower cholesterol in plasma, reduction in lipid deposits in the liver and muscle, and lower hepatic triglyceride levels

improved glucose tolerance ( J:216593 )

• mice exhibit improved glucose tolerance in the oral glucose tolerance test

increased insulin sensitivity ( J:216593 )

• mice exhibit improved insulin tolerance

• the dose of insulin necessary to induce glucose transport and to reach a plateau are lower in adipocytes, suggesting increased insulin sensitivity

decreased circulating adiponectin level ( J:216593 )

abnormal lipid level ( J:216593 )

• lipid deposits in liver and muscle are decreased

increased glycerol level ( J:216593 )

• basal glycerol release is increased in epididymal fat pad adipocytes, indicating enhanced lipolysis

decreased liver triglyceride level ( J:216593 )

decreased skeletal muscle triglyceride level ( J:216593 )

• in the gastrocnemius muscle

abnormal carbohydrate metabolism ( J:216593 )

• mice exhibit improved carbohydrate metabolism

enhanced lipolysis ( J:216593 )

• basal glycerol release is increased in epididymal fat pad adipocytes, indicating enhanced lipolysis

integument

decreased subcutaneous adipose tissue amount ( J:216593 )

• subcutaneous white adipose tissues are smaller

liver/biliary system

decreased liver triglyceride level ( J:216593 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome with multiple lentigines		DOID:14291	OMIM:PS151100	J:216593