Dissecting genetic control of autoimmunity in NOD congenic mice

Abstract

My lab investigates genetic control of autoimmune disease and autoimmune phenotypes using a series of nonobese diabetic (NOD) congenic mice. NOD congenic mice have regions from B6/B10 introgressed onto the NOD genetic background, which reduces the severity/incidence of autoimmune diabetes. We have demonstrated, however, that while diabetes is reduced, other autoimmune phenotypes and diseases arise in NOD congenic mice. Mapping the genomic regions responsible for these phenotypes has produced novel insights into genetic control of autoimmunity. This review will illustrate some of the genetically controlled phenotypes we have investigated, which shed light upon autoimmune features relevant to human type 1 diabetes, systemic lupus erythematosus, and primary biliary cirrhosis.

Fig. 1

A congenic mapping approach to analyzing genetic control of autoimmune disease. The dark vertical bars represent B6/B10 genetic intervals on the NOD background in NOD.c3c4 and related congenic mice. The scale is in megabases. Representative microsatellite markers demarcate the boundaries of the intervals. Positions of Insulin dependent diabetes (Idd) loci and the newly defined autoimmune biliary (abd) locus are shown in italics. The relative penetrance of ABD in each strain is shown in the chart on the bottom, which also depicts the genetic intervals carried in each strain.