Psoriasiform Dermatitis Susceptibility in Itgb2tm1Bay PL/J Mice Requires Low-Level CD18 Expression and at Least Two Additional Loci for Progression to Severe Disease

摘要

>Itgb2^>tm1Bay PL/J mice express low levels of the β2 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 × 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 × 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.