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(American Journal of Pathology. 2003;163:197-202.)
© 2003 American Society for Investigative Pathology

Psoriasiform Dermatitis Susceptibility in Itgb2^tm1Bay PL/J Mice Requires Low-Level CD18 Expression and at Least Two Additional Loci for Progression to Severe Disease

Shayne C. Barlow^*, Robert G. Collins, Nigel J. Ball, Casey T. Weaver, Trenton R. Schoeb^* and Daniel C. Bullard^*

From the Departments of Genomics and Pathobiology^* and Pathology, The University of Alabama at Birmingham, Birmingham, Alabama; the Department of Pediatrics, Section of Leukocyte Biology, Baylor College of Medicine, Houston, Texas; and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, Canada

Itgb2^tm1Bay PL/J mice express low levels of the ß₂ integrins and, unlike Itgb2^tm1Bay C57BL/6J mice, spontaneously develop psoriasiform dermatitis with several similarities to human psoriasis. To define the genetic requirements for skin disease susceptibility we analyzed more than 500 F2 progeny from an Itgb2^tm1Bay (PL/J x C57BL/6J) intercross. We found that 23.5% developed chronic inflammatory skin disease, although significant differences in severity were observed. Another CD18 mutation, Itgb2^tm2Bay, has now been generated that completely eliminates CD18 expression. Surprisingly, of 10 Itgb2^tm2Bay homozygote PL/J N4 mice generated, none showed clinical or histopathological evidence of disease. However, Itgb2^tm1Bay/Itgb2^tm2Bay PL/J mice developed dermatitis indistinguishable from Itgb2^tm1Bay PL/J mice. In addition, approximately half of Itgb2^tm1Bay/Itgb2^tm2Bay (C57BL/6J x PL/J)F1 mice were found to develop mild psoriasiform dermatitis identical to the early stages of disease seen in Itgb2^tm1Bay PL/J mice. Collectively, these results suggest a complex inheritance pattern of psoriasiform dermatitis in this model that involves lowered, but not absent, CD18 expression and at least two additional PL/J loci for the development of severe disease. The susceptibility allele can act in either a heterozygous or homozygous state, dependent on the level of CD18 expression.

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