F15 ALOPECIA AREATA-LIKE HAIR LOSS IN C3H/HeJ MICE: A COMPLEX POLYGENIC AUTOIMMUNE DISEASE.  

¹Sundberg JP, ²Levin E, ²McElwee K, ³King LE, ¹Cox G, ¹Churchill G.  ¹The Jackson Laboratory, Bar Harbor, ME, U.S.A.; ²Dept. Dermatology, Philipp University, Marburg, Germany; and ³Dept. Dermatology, Vanderbilt University, Nashville, TN, U.S.A.

C-3H/HeJ inbred laboratory mice develop a low frequency (approaching 20%) of a spontaneous alopecia areata-like disease as they age.  This is a highly phylogenetically conserved disease, implying that similar or identical disease mechanisms may be found in all affected species.  Our goal was to define the genetic basis of alopecia areata using a mouse model.  Initial intercrosses between C3H/HeJ and C57BL/6J yielded 10% affected females and 2% affected males.  A second intercross study aged only females and provided nearly 100 affected F2 hybrid mice.  Genome wide screens, using simple sequence length polymorphisms between parental strains, identified three statistically significant loci associated with alopecia areata and 10 loci that approached significance.  One locus was on mouse Chromosome 17 within the H2 complex, essentially on top of the orthologous region for human HLADR and HLADQ, significant loci in human alopecia areata. The second locus, not surprisingly, was on mouse Chromosome X.  A third was on mouse Chromosome 1. Candidate genes are being defined and the other loci are being resolved by high density mapping strategies.