Abstract:Objective To develop a diabetic mouse model to investigate metabolic changes of blood glucose level and body weight in the MKR mouse,a model in which expression of a dominant-negative IGF-I receptor in the skeletal muscle leads to systemic insulin resistance and diabetes.Methods\ MKR mice were received from the National Institutes of Health,USA,and genotyped by a specific PCR reaction using tail DNA.These mice were followed up for blood glucose level and body weight once a week from 1 to 16 weeks of age.The serum insulin level and glucose tolerance were determined at two months,using wild-type Kunming mice or C57 mice as controls.Results\ The offspring of MKR mice exhibited stable transgenic hereditary.These mice were hyperglycaemic from 3 weeks of age onward.The body weight increase slowed down after 4 month.There was 20-fold hyperinsulinemia in MKR vs.wild-type littermates,and very significant glucose intolerance in 2month-old MKR mice.The hyperglycemia is more severe in male especially older male MKR mice,than their female counterparts.Conclusion\ We have estabolished the MKR model,set up a PCR reaction to genotype and revealed sexual dimorphic changes in the type 2 diabetes.