EPIDERMAL DENDRITIC CELL-POPULATIONS IN THE FLAKY SKIN MUTANT MOUSE

Flaky skin (gene symbol: fsn) is an autosomal recessive mouse mutation that causes pathologic changes in the skin yielding a papulosquamous disease resembling human psoriasis. Preliminary studies of epidermal s heets from foot pads of fsn/fsn mice stained for Ia+ Langerhans cells (LC) or Thy-1+ dendritic epidermal cells (Thy-1+ DEC) indicated a rise in LC numbers at the time of weaning, when the skin lesion becomes cl inically evident. To further investigate this observation, epidermal s heets were obtained from the ear, dorsal skin, and foot pads from repl icates of 6 female mice (both mutants and normal littermates) on weekl y intervals from birth to 8 weeks of age. Dorsal skin epidermal thickn ess was quantitated by computer assisted image analysis and found to b e significantly thickened from one week onward in the mutant mice. Usi ng immunofluorescence microscopy, epidermal dendritic cell numbers wer e determined following staining with antibodies for the following mark ers: Ia, NLDC-145, and S-100 (for LC) or Thy 1.2 and asialo-GM1 (for T hy-1+ DEC). Use of all 5 markers to evaluate skin from 3 different loc ations yielded a subtle but significant increase in LC and Thy-1+ DEC in flaky skin mice. Of the three sites evaluated, the dorsal skin and ear epidermal sheets were most informative, which corresponded to the degree of pathological involvement. Mice doubly homozygous for fsn and for the severe combined immunodeficiency (scid) mutation developed th e psoriasiform dermatitis. Bone marrow grafts from fsn/fsn homozygotes to homozygous scid/scid mice reproduce the skin lesion. These studies suggest that the psoriasiform dermatitis in the flaky skin mouse muta tion is associated with abnormalities at the level of hematopoietic pr ogenitor cells.