[Positional cloning of susceptibility genes for non-insulin-dependent diabetes mellitus]

Although studies of families and twin studies have demonstrated that non-insulin-dependent diabetes mellitus (NIDDM) has a strong genetic component, the genes responsible for the common forms of NIDDM are largely unknown, due to the complex and heterogeneous nature of the disease. To study the genetics of NIDDM, we used an inbred animal model of NIDDM, the NSY mouse, in which NIDDM spontaneously develops in an age-dependent manner. The inheritance pattern of glucose tolerance, fasting insulin levels, insulin response to glucose, body mass index, and epididymal fat pad weight in F 1 hybrids of NSY with control C3H/He mice suggested the different modes of inheritance in these phenotypes. Multipoint linkage analysis of glucose tolerance in F2 mice with microsatellite markers throughout the genome mapped at least three loci on different chromosomes. Positional cloning of susceptibility genes for NIDDM in NSY mice may increase our understanding of the genetics and etiology of human NIDDM and may lead to more effective methods for prevention and intervention.