CRISPR-Cas9-mediated generation of obese and diabetic mouse models.

Mouse models of obesity (oblob) and diabetes (dbldb) in which the leptin (Lep) and leptin receptor (Lepr) genes have been mutated, respectively, have contributed to a better understanding of human obesity and type 2 diabetes and to the prevention, diagnosis, and treatment of these metabolic diseases. In this study, we report the first CRISPR-Cas9-induced Lep and Lepr knockout (KO) mouse models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr KO mouse models showed phenotypic disorders nearly identical to those found in oblob and dbldb mice, such as an increase in body weight, hyperglycemia, and hepatic steatosis. Thus, Cas9-generated Lep and Lepr KO mouse lines will be easier for genotyping, to maintain the lines, and to use for future obesity and diabetes research.