POLYGENIC MOUSE MODEL OF PSORIASIFORM SKIN-DISEASE IN CD18-DEFICIENT MICE

Previously, a hypomorphic mutation in CD18 was generated by gene targe ting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, an d delays in transplantation rejection, When this mutation was backcros sed onto the PL/J inbred strain, virtually all homozygous mice del elo ped a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth, The disease was characterized by erythema, hair lo ss, and the development of scales and crusts, The histopathology revea led hyperplasia of the epidermis, subcorneal microabscesses, orthohype rkeratosis, parakeratosis, and lymphocyte exocytosis, which are featur es in common with human psoriasis and other hyperproliferative inflamm atory skin disorders, Repetitive cultures failed to demonstrate bacter ial or fungal organisms potentially involved in the pathogenesis of th is disease, and the dermatitis resolved rapidly after subcutaneous adm inistration of dexamethasone. Homozygous mutant mice on a (PL/J x C57B L/6J) F-1 background did not develop the disease and backcross experim ents suggest that a small number of genes (perhaps as fen as one), In addition to CD18, determine susceptibility to the disorder, This pheno type provides a model for inflammatory skin disorders, may have genera l relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the beta(2) integrins in inflamma tory processes.