Linkage on Chromosome 3 of Autoimmune Diabetes and Defective Fc Receptor for IgG in NOD Mice

A congenic, non-obese diabetic (NOD) mouse strain that contains a segment of chromosome 3 from the diabetes-resistant mouse strain B6.PL-Thy-1$^a$ was less susceptible to diabetes than NOD mice. A fully penetrant immunological defect also mapped to this segment, which encodes the high-affinity Fc receptor for immunoglobulin G (IgG), FcγRI. The NOD Fcgr1 allele, which results in a deletion of the cytoplasmic tail, caused a 73 percent reduction in the turnover of cell surface receptor-antibody complexes. The development of congenic strains and the characterization of Mendelian traits that are specific to the disease phenotype demonstrate the feasibility of dissecting the pathophysiology of complex, non-Mendelian diseases.