Phenotypes Associated with This Genotype

Genotype
MGI:3618625

• Allelic Composition: Nos3^tm1Unc/Nos3^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd

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

mortality/aging

premature death ( J:102136 )

• 50% of males die by 21 months of age, however female survival is similar to wild-type

growth/size/body

increased heart weight ( J:102136 )

• large increase in heart weight and heart weight to body weight ratio in males at 21 months of age and a smaller increase in females

cardiac hypertrophy ( J:102136 )

• at 21 months of age, males have a large increase and females have a slight increase in heart size

decreased body weight ( J:102136 )

• both males and females weight less than wild-type at 21 months of age

cardiovascular system

abnormal heart morphology ( J:102136 )

• at 21 months of age, males exhibit wall thinning of the heart while females display an increase in wall thickness of the heart

abnormal interventricular septum morphology ( J:102136 )

• females, but not males, exhibit a significant increase in diastolic septal wall thickness and to a lesser degree in the posterior wall

• males exhibit a decrease in interventricular septum thickening at 21 months of age

increased heart weight ( J:102136 )

• large increase in heart weight and heart weight to body weight ratio in males at 21 months of age and a smaller increase in females

cardiac hypertrophy ( J:102136 )

• at 21 months of age, males have a large increase and females have a slight increase in heart size

decreased heart left ventricle posterior wall thickness ( J:102136 )

• males at 21 months of age, but not at 5.5 months, exhibit a decrease in left ventricular posterior wall thickness

dilated heart left ventricle ( J:102136 )

• left-ventricular end-systolic chamber dilation (LVESD) is increased about 45% in homozygous males compared to 25% in wild-type males at 21 months of age; no differences seen in females

• left ventricular mass (LVMASS) is increased in both males and females at 21 months of age

• ratio between LVMASS and LV volume is increased in 21 month old males

decreased cardiac muscle contractility ( J:102136 )

• males, but not females, exhibit a marked decrease in ejection fraction and shortening fraction at 21 months of age

increased heart rate ( J:102136 )

• heart rate is increased in males at 5.5 months of age but not at 21 months of age

• heart rate is normal in females at 5.5 months of age but remains elevated at 21 months of age and does not fall with age as in wild-type

abnormal systemic arterial blood pressure ( J:102136 )

increased systemic arterial blood pressure ( J:102136 )

• mean blood pressure is significantly elevated in both males and females at 5.5 months of age

• at 21 months of age, females, but not males, continue to exhibit increased mean blood pressure

hypertension ( J:102136 , J:103153 )

• females are hypertensive at 7 months of age and maintain the elevated pressure at 21 months of age, however do not exhibit any contractile dysfunction (J:102136)

• arterial hypertension (J:103153)

increased systemic arterial diastolic blood pressure ( J:102136 )

• elevated at 5.5 months of age in both males and females

• at 21 months of age, females, but not males, continue to exhibit an increased diastolic blood pressure

increased systemic arterial systolic blood pressure ( J:102136 )

• elevated at 5.5 months of age in both males and females

• at 21 months of age, females, but not males, continue to exhibit an increased systolic blood pressure

decreased vasodilation ( J:103153 )

• insulin stimulation of muscle blood flow is about 40% smaller than in wild-type

homeostasis/metabolism

abnormal blood homeostasis ( J:103153 )

• plasma nitrite and nitrate concentrations are about 60% lower than in wild-type, indicating a defect of vascular NO production

increased circulating cholesterol level ( J:103153 )

• insulin-resistant homozygotes have 50% higher plasma levels of cholesterol

increased circulating free fatty acids level ( J:103153 )

• insulin-resistant homozygotes have a 2-fold elevation of free fatty acid

increased circulating triglyceride level ( J:103153 )

• insulin-resistant homozygotes have a 2-fold elevation of triglycerides

hyperlipidemia ( J:103153 )

abnormal glucose homeostasis ( J:103153 )

• glucose infusion rate, glucose turnover rate, and glucose clearance rate are 30-40% lower during a hyperinsulinemic euglycemic clamp study

• basal and insulin-stimulated glucose transport in isolated skeletal muscle is about 40% lower than in wild-type

increased circulating insulin level ( J:103153 )

• fasting plasma insulin concentration is elevated almost 2-fold

insulin resistance ( J:103153 )

• fasting hyperinsulinemia and glucose infusion rates during euglycemic clamp studies are 40% lower than in wild-type

muscle

decreased cardiac muscle contractility ( J:102136 )

• males, but not females, exhibit a marked decrease in ejection fraction and shortening fraction at 21 months of age

decreased vasodilation ( J:103153 )

• insulin stimulation of muscle blood flow is about 40% smaller than in wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
essential hypertension		DOID:10825	OMIM:145500 OMIM:603918 OMIM:604329 OMIM:607329 OMIM:608742 OMIM:610261 OMIM:610262 OMIM:610948 OMIM:611014	J:103153