ABSTRACT

This chapter is meant to serve as a “primer” for use of two of the most intensively-studied monogenic obesity mutations in the mouse, obese (ob) and diabetes (db). The previous observations that both mutations, although mapping to separate chromosomes, produced nearly identical obesity/diabetes syndromes when studied on a common inbred background, coupled with the results of parabiosis studies (Coleman, 1973, 1978), suggested that the two mutations affected a common pathway. This has been confirmed by recent discoveries showing the ob mutation to be a defect in the gene encoding leptin, and the db mutation to be a defective leptin receptor. Several recent reviews contrast these two mutations with other monogenic obesity-producing genes in the mouse (Kim et al., 1998; McIntosh and Pederson, 1999). In the rat, the fatty (fa) mutation on Chromosome 5 (and its allele, corpulent, cp) are homologs of the mouse db mutation (Chua et al., 1996a, 1996b). This chapter will help to integrate the extensive early literature describing the physiologic, biochemical, and behavioral effects of the mouse mutations with the more current information gained from the molecular information and the availability of recombinant leptin protein.