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.
Itgb2(tm1Bay) PL/J mice express low levels of the beta(2) 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.
Barlow
Shayne C
SC
Department of Genomics and Pathobiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Collins
Robert G
RG
Ball
Nigel J
NJ
Weaver
Casey T
CT
Schoeb
Trenton R
TR
Bullard
Daniel C
DC
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism*; D003872:Dermatitis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology
D018821:CD18 Antigens