Generation of PKO mice. A: A schematic representation of gene targeting strategies to generate conditional SH2B1 KO mice. Squares represent individual exons, and the first is a noncoding exon. B: Pancreatic extracts were prepared from SH2B1f/f, Pdx1-Cre, and PKO male mice (12 weeks) and immunoprecipitated (IP) and immunoblotted (IB) with anti-SH2B1 antibody. Pancreatic extracts were also immunoblotted with anti–β-tubulin antibody. C: Tissue extracts were immunoprecipitated and immunoblotted with anti-SH2B1 antibody. D: Body weights of chow-fed male mice at 8 (control: n = 7; PKO: n = 8) and 18 (control: n = 4; PKO: n = 5) weeks of age. E. Body weights of male mice fed an HFD (45% fat) at 8 weeks of age. Control group includes both SH2B1f/f (n = 17–29) and Pdx1-Cre (n = 4–11) mice; PKO: n = 10–21. Con, control; FRT, Flp-recombinase recognition; TK, thymidine kinase.