A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.
Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and the development of scales and crusts. The histopathology revealed hyperplasia of the epidermis, subcorneal microabscesses, orthohyperkeratosis, parakeratosis, and lymphocyte exocytosis, which are features in common with human psoriasis and other hyperproliferative inflammatory skin disorders. Repetitive cultures failed to demonstrate bacterial or fungal organisms potentially involved in the pathogenesis of this disease, and the dermatitis resolved rapidly after subcutaneous administration of dexamethasone. Homozygous mutant mice on a (PL/J x C57BL/6J)F1 background did not develop the disease and backcross experiments suggest that a small number of genes (perhaps as few as one), in addition to CD18, determine susceptibility to the disorder. This phenotype provides a model for inflammatory skin disorders, may have general relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the beta2 integrins in inflammatory processes.
Bullard
D C
DC
Department of Molecular, Baylor College of Medicine, Houston, TX 77030, USA.
Scharffetter-Kochanek
K
K
McArthur
M J
MJ
Chosay
J G
JG
McBride
M E
ME
Montgomery
C A
CA
Beaudet
A L
AL
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology*; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000627:therapeutic use; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D018821:CD18 Antigens; D005938:Glucocorticoids; D003907:Dexamethasone