title: Identification of susceptibility loci for skin disease in a murine psoriasis model.
abstract: Psoriasis is a frequently occurring inflammatory skin disease characterized by thickened erythematous skin that is covered with silvery scales. It is a complex genetic disease with both heritable and environmental factors contributing to onset and severity. The CD18 hypomorphic PL/J mouse reveals reduced expression of the common chain of beta(2) integrins (CD11/CD18) and spontaneously develops a skin disease that closely resembles human psoriasis. In contrast, CD18 hypomorphic C57BL/6J mice do not demonstrate this phenotype. In this study, we have performed a genome-wide scan to identify loci involved in psoriasiform dermatitis under the condition of low CD18 expression. Backcross analysis of a segregating cross between susceptible CD18 hypomorphic PL/J mice and the resistant CD18 hypomorphic C57BL/6J strain was performed. A genome-wide linkage analysis of 94 phenotypically extreme mice of the backcross was undertaken. Thereafter, a complementary analysis of the regions of interest from the genome-wide screen was done using higher marker density and further mice. We found two loci on chromosome 10 that were significantly linked to the disease and interacted in an additive fashion in its development. In addition, a locus on chromosome 6 that promoted earlier onset of the disease was identified in the most severely affected mice. For the first time, we have identified genetic regions associated with psoriasis in a mouse model resembling human psoriasis. The identification of gene regions associated with psoriasis in this mouse model might contribute to the understanding of genetic causes of psoriasis in patients and pathological mechanisms involved in development of disease.
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, D-89081 Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kess
authors.forename: Anna-Karin B
authors.initials: AK
authors.lastname: Lindqvist
authors.forename: Thorsten
authors.initials: T
authors.lastname: Peters
authors.forename: Honglin
authors.initials: H
authors.lastname: Wang
authors.forename: Jan
authors.initials: J
authors.lastname: Zamek
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
authors.forename: Karl W
authors.initials: KW
authors.lastname: Broman
authors.forename: Robert
authors.initials: R
authors.lastname: Blakytny
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008126:Lod Score; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics*; D040641:Quantitative Trait Loci
chemical_list: D018821:CD18 Antigens