IDENTIFICATION AND MAPPING TO CHROMOSOME-1 OF A SUSCEPTIBILITY LOCUS FOR PERIINSULITIS IN NONOBESE DIABETIC MICE

INSULIN-DEPENDENT diabetes mellitus (IDDM) is a polygenic disease caused by autoimmune destruction of insulin-producing beta-cells in the islets of Langerhans 1,2. Its onset is preceded by a long and variable period in which lymphoid cells infiltrate the pancreas but first remain outside the islets (peri-insulitis) before invading them (insulitis) 3-7. Among susceptibility loci, only the major histocompatibility complex (MHC) has been clearly assigned 8-12. Genetic study of the nonobese diabetic (NOD) mouse model for insulin-dependent diabetes mellitus has revealed genetic linkage of insulitis and of early onset diabetes with two non-MHC loci mapping to chromosome 3 and 11 respectively 13. Here we report a close association of periinsulitis with a third non-MHC locus mapping to chromosome 1. Successive stages in the progression of diabetic disease thus appear to be controlled by distinct genes or sets of genes.