Abstract: Objective To meet the need of study and development in diabetes mellitus in China, the Lepr^tm1Srcmo gene knockin mouse model was established. Methods Using ET cloning, homologous recombination, microinjection technology, the Lepr gene knockin mouse with a point mutation (G to T) in 3’UTR of lepr 004 mRNA was established. Body weights and plasma glucose were measured, and the mice of 8 and 13 months old were sacrificed for detection on the serum biochemistry parameters including insulin, glucose, TG, TC, HDL, LDL, AST, ALT, ALP, UA and so on. All the datum of Lepr^tm1Srcmomice were compared with age-matched wild type (WT) mice in statistics. Pathological changes between Lepr^tm1Srcmo and WT of hepatic and kidney tissues were observed under microscope. Results PCR and sequence analysis confirmed the mutation of lepr gene in the knockin mouse. Preliminarily phenotypic observations show that Lepr^tm1Srcmomice develop obesity at about 4 weeks of age and hyperinsulinemia, hyperglycemia, lipid metabolism disorder, liver and kidney dysfunction is serious on the Lepr^tm1Srcmomale mice of 8 months. At the age of 13 months blood glucose levels reduce to normal and other phenotypes are still existed. From the pathological analysis, the hepatocyte swelling and macrovacuolar steatosis were also observed in the Lepr^tm1Srcmo male mice. Conclusion The Lepr^tm1Srcmo mice could be used as an appropriate disease model of type 2 diabetes mellitus for research on the etiology, pathogenesis and drug treatment.

Key words: Lepr gene, Gene knockin mouse, Type 2 Diabetes