This allele interacts with Psrs6 on chromosome 4. Homozygosity for PL/J-derived alleles at both Psrs4 and Psrs6 confers increased susceptibility to psoriasis.
Mapping and Phenotype information for this QTL, its variants and associated markers
Linkage analysis was performed on 343 animals from a (PL/J-Itgb2<tm1Bay> x C57BL/6J-Itgb2<tm1Bay>)F1 x PL/J-Itgb2<tm1Bay> backcross to identify QTLs associated with psoriasis susceptibility. Parental strain PL/J-Itgb2<tm1Bay> is CD18 hypomorphic and displays spontaneous development of a skin disease resembling psoriasis. Parental strain C57BL/6J-Itgb2<tm1Bay> is CD18 hypomorphic and does not develop psoriasis. Genome scan was performed using 83 microsatellite markers at an average resolution of 17 cM.
Significant linkage to psoriasis time of onset and severity in CD18 hypomorphic backcross animals mapped to 18 cM on mouse Chromosome 10 near D10Mit86 and D10Mit214 (LOD=10.2). This locus is named Psrs1 (psoriasis susceptibility 1). PL/J-derived allelesat Psrs1 promoted psoriasiform skin disease in backcross animals. A second locus, Psrs2 (psoriasis susceptibility 2), at 63 cM near D10Mit233 and D10Mit14 is linked to psoriasis susceptibility and severity. PL/J-derived alleles at Psrs2 confer increased psoriasis susceptibility and severity in CD18 hypomorphic backcross animals. Both Psrs1 and Psrs2 exhibit additive inheritance and do not appear to interact.
Psrs3 (psoriasis susceptibility 3) mapped to 41.5 cM on mouse Chromosome 6 near D6Mit67 (LOD=3.1)in linkage to psoriasis time of onset. This locus also exhibits suggestive linkage to psoriasis susceptibility (LOD=1.6) and severity (LOD=1.4). PL/J-derived alleles at Psrs3 promote psoriasis in CD18 hypomorphic backcross animals. The Psrs3 QTL intervalis flanked by D6Mit4 (33.5 cM) and D6Mit25 (65 cM).
Significant linkage to psoriasis severity, named Psrs4 (psoriasis susceptibility 4), mapped to 25 cM (46 Mb) on mouse Chromosome 1 near D1Mit236. A second locus named Psrs5 (psoriasis susceptibility 5)islinked to psoriasis severity and mapped to 107 cM (191 Mb) near Tgfbm3 (formerly D1Mit17) and D1Mit292. PL/J-derived alleles at Psrs4 and Psrs5 confer increased disease severity.
Psrs6 (psoriasis susceptibility 6) is located at 66.6 cM on mouse Chromosome 4 near D4Mit170. This locus interacts with Psrs4 on mouse Chromosome 1. Animals homozygous for PL/J-derived alleles at both Psrs4 and Psrs6 exhibit significantly increased psoriasis susceptibility.
Significant linkage to psoriasis severity, designated Psrs7 (psoriasissusceptibility 7), mapped to 22 cM - 24 cM (44 Mb - 46 Mb) on mouse Chromosome 18 near D18Mit194 and D18Mit35. PL/J-derived alleles at Psrs7 confer increased psoriasis severity.