LYMPHADENOPATHY, ELEVATED SERUM IGE LEVELS, AUTOIMMUNITY, AND MAST-CELL ACCUMULATION IN FLAKY SKIN MUTANT MICE

The autosomal recessive mutation ''flaky skin'' (fsn) causes pleiotrop ic abnormalities in the immune and hematopoietic systems accompanied b y pathologic changes in the skin. Homozygotes (fsn/fsn) showed increas ed size and histological alterations in the spleen and lymph nodes. Ab normalities in lymphoid architecture of the spleen in fsn/fsn mice wer e accompanied by marked increases in total numbers of B cells, macroph ages, and immature erythroid cells. Splenic B cells displayed elevated MHC class II expression. Serum IgE levels were greater than 100 mu g/ ml by 10 weeks of age, representing > 7000-fold increase compared with normal littermates. This increased IgE level was associated with elev ated IL-4 production by spleen cells and with increased amounts of ser um IL-4. Serum IgM, IgG1, and IgG2b levels were also increased in fsn/ fsn mice while IgG3 was decreased. Autoimmunity in fsn/fsn mice was ev idenced by glomerulonephritis accompanied by immune complex deposition in the kidneys, increased serum blood urea nitrogen levels, and the p resence of circulating anti-double-stranded DNA autoantibodies. Pathol ogical changes in the skin of fsn/fsn mice were characterized by epide rmal hyperplasia and mixed dermal inflammation. Increased numbers of m ast cells were also observed in the dermis of the truncal skin as well as in the epithelial stomach. These marked immunological abnormalitie s suggest that the fsn locus encodes a major immunoregulatory molecule important in multiple immune and hematopoietic functions.