Mouse Genome Informatics
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
• fasting serum leptin levels are elevated in older mutants
• 180% increase in glucose transport into the epididymal adipose depot
• develop hyperinsulinemia with age; fasting serum insulin levels are elevated 2-fold at 1-2 months of age and 3-fold at 10 months of age
• develop progressive glucose intolerance with age
• insulin-stimulated glycogen synthesis is reduced
• in a non-fasting state, mutants show a reduction in glycogen stores in adipose tissue (54% less), liver (42% less), heart (48% less), and skeletal muscle (26% less)
• in a fasted state, mutants show a 25% reduction in hepatic and heart glycogen
• develop insulin resistance with age
• skeletal muscle of 18 month old mutants shows 30% increase in triglyceride content
• serum levels of fasting, but not non-fasting, triglycerides are increased by about 32% at 18 months of age
• decrease in glycogen synthase activity in 1-2 month old mutants

• glucose uptake by white fiber quadriceps muscle is reduced by 35% in 3-4 month old mutants, however uptake into mixed fiber gastrocnemius muscle is not altered

cardiovascular system
• 25% increase in heart weight and heart/body weight ratio is seen in aged mutants

Mouse Models of Human Disease
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:83297