067 Genetic basis of alopecia areata in C3H/HeJ Mice

Sundberg JP1, Levin E1, Boggess D1, Silva K1, Churchill G1, McElwee KJ1, King LE2, and Cox G1. The Jackson Laboratory, Bar Harbor, ME1; Vanderbilt University and the Nashville VA Medical Centers, Nashville, TN2

Alopecia areata is a relatively common disfiguring autoimmune disease that targets hair follicles in the actively growing anagen phase of the hair cycle. Alopecia areata is often associated with many other systemic autoimmune diseases. An alopecia areata-like phenotype occurs spontaneously in the C3H/HeJ inbred mouse strain as a complex polygenic trait with low penetrance. An extensive intercross breeding study between C3H/HeJ and C57BL/6J mice and subsequent genome wide screening has revealed at least 4 genetic loci involved in spontaneous mouse alopecia areata. The most significant locus is on Chromosome 17 at 18.8 cM. This region of the mouse H2 complex is homologous with the human HLA locus. In human alopecia areata, two loci have been linked to HLA-DR and HLA-DQ. The homologous mouse loci are located at 18.64 and 18.68 cM, respectively, on mouse Chromosome 17, less than 0.2 cM from the most significant locus found in this mapping study for mouse alopecia areata. Additional loci of lower significance were identified on mouse Chromosomes 1, 15, and X. The mouse results indicate potential associated human AA loci in these locations. Genome wide screening of rodent alopecia areata models and use of comparative mouse-human genome maps may confirm previously defined human AA associated susceptibility genes and may identify new candidate gene loci for further investigation in human patients.