The C57BL/6NCrl‐lb Mouse: A New Model for Metabolic Syndrome

Abstract

A novel mutation, lb in the leptin receptor gene, has been identified in C57 BL/6NCrl mice from a barrier production colony at Charles River Laboratories. Animals heterozygous for the mutation exhibit a wild-type phenotype. The mutant lb/lb mice have been characterized by metabolic, genetic, and phenotypic methods. The lb/lb mutant mice display key features of the metabolic syndrome; they are markedly obese, and hyperinsulinemic by 8 weeks of age, with insulin levels exceeding 200 ng/ml by 18 weeks of age. When compared to other models of metabolic syndrome, mutant lb mice also had hyperglycemia greater than that of the B6.V-Lepob/J (ob) mouse, but less than the BKS.Cg-m+/+Leprdb/J (db). Like db mice, the lb mice had increased leptin levels, higher in fact, than db mice at 17–18 weeks of age. Genetic complementation studies crossing mice heterozygous for the lb mutation with Leprdb heterozygous mice produced 25% fat and 75% lean offspring, confirming that the mutations are in the same gene. DNA sequence analysis of the leptin receptor coding sequence in lb mice has not revealed any mutations. These mice have characteristics of the ob and the db mice. This distinct phenotype makes these mice an additional model for drug discovery studies of metabolic syndrome.