Psoriasiform dermatitis susceptibility in Itgb2tm1Bay PL/J mice requires low-level CD18 expression and at least two additional loci for progression to severe disease

Academic Article

Abstract

  • Itgb2 PL/J mice express low levels of the β integrins and, unlike Itgb2 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 (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 has now been generated that completely eliminates CD18 expression. Surprisingly, of 10 Itgb2 homozygote PL/J N4 mice generated, none showed clinical or histopathological evidence of disease. However, Itgb2 /Itgb2 PL/J mice developed dermatitis indistinguishable from Itgb2 PL/J mice. In addition, approximately half of Itgb2 /Itgb2 (C57BL/6J x PL/J)F1 mice were found to develop mild psoriasiform dermatitis identical to the early stages of disease seen in Itgb2 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. tm1Bay tm1Bay tm1Bay tm2Bay tm2Bay tm1Bay tm2Bay tm1Bay tm1Bay tm2Bay tm1Bay 2
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 26703675
  • Author List

  • Barlow SC; Collins RG; Ball NJ; Weaver CT; Schoeb TR; Bullard DC
  • Start Page

  • 197
  • End Page

  • 202
  • Volume

  • 163
  • Issue

  • 1