POLYGENIC CONTROL OF AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE

Partial exclusion mapping of the nonobese (NOD) diabetic mouse genome has shown linkage of diabetes to at least five different chromosomes. We have now excluded almost all of the genome for the presence of susc eptibility genes with fully recessive effects and have obtained eviden ce of linkage of ten distinct loci to diabetes or the prediabetic lesi on, insulitis, indicative of a polygenic mode of inheritance. The rela tive importance of these loci and their interactions have been assesse d using a new application of multiple polychotomous regression methods . A candidate disease gene, interleukin-2 (Il-2), which is closely lin ked to insulitis and diabetes, is shown to have a different sequence i n NOD, including an insertion and a deletion of tandem repeat sequence s which encode amino acid repeats in the mature protein.