Mouse Genome Informatics
hm
    Nos3tm1Unc/Nos3tm1Unc
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 50% of males die by 21 months of age, however female survival is similar to wild-type

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

cardiovascular system
• at 21 months of age, males exhibit wall thinning of the heart while females display an increase in wall thickness of the heart
• 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
• 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
• at 21 months of age, males have a large increase and females have a slight increase in heart size
• 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
• males at 21 months of age, but not at 5.5 months, exhibit a decrease in left ventricular posterior wall
• insulin stimulation of muscle blood flow is about 40% smaller than in wild-type
• males, but not females, exhibit a marked decrease in ejection fraction and shortening fraction at 21 months of age
• 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
• 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
• 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)
• 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
• 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

homeostasis/metabolism
• plasma nitrite and nitrate concentrations are about 60% lower than in wild-type, indicating a defect of vascular NO production
• insulin-resistant homozygotes have 50% higher plasma levels of cholesterol
• insulin-resistant homozygotes have a 2-fold elevation of free fatty acid
• insulin-resistant homozygotes have a 2-fold elevation of triglycerides
• 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
• fasting plasma insulin concentration is elevated almost 2-fold
• fasting hyperinsulinemia and glucose infusion rates during euglycemic clamp studies are 40% lower than in wild-type

muscle
• insulin stimulation of muscle blood flow is about 40% smaller than in wild-type
• males, but not females, exhibit a marked decrease in ejection fraction and shortening fraction at 21 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Hypertension, Essential 145500 J:103153