Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  10
• Reference
  J:134251 Wang H, et al., A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model. J Immunol. 2008 Apr 15;180(8):5520-9
• ID
  MGI:3790700

Genes

Gene	Assay Type
Psrs1	resistance/susceptibility
D10Mit126	PCR
D10Mit194	PCR

Notes

• Experiment
  Psoriasis susceptibility QTLs Psrs1 (18 cM, chr10) and Psrs3 (41.5 cM chr6) were previously identified in a backcross derived from PL/J-Itgb2^tm1Bay and C57BL/6J-Itgb2^tm1Bay. Parental strain PL/J-Itgb2^tm1Bay is CD18 hypomorphic and displays spontaneous development of a skin disease resembling human psoriasis. In contrast, the same CD18 hypomorphic allele, Itgb2^tm1Bay, on a C57BL/6J genetic background does not result in psoriasis.
  
  The current study confirmed and localized Psrs1 (aka Pds1) usingcongenic line analysis. When a PL/J-derived genetic interval surrounding Prsr1 is introgressed onto a C57BL/6J-Itgb2^tm1Bay psoriasis-resistant background, the resulting congenic animals recapitulate the psoriasis-susceptible phenotype of PL/J-Itgb2^tm1Bay. Analysis of four congenic lines narrowed the Psrs1 interval to a 9 cM region between D10Mit126 (21 cM) and D10Mit194 (29 cM). This region contains 46 known genes. Authors mention Cd24a (26 cM), Gja1 (29 cM) and Fyn (25 cM) as some potential candidatesfor Psrs1. The Psrs1 locus is syntenic to human Chromosome 6q16 and 6q21-q24. Although no psoriasis QTLs have been mapped to these regions in humans, autoimmune type 1 diabetes and rheumatoid arthritis have been associated with human 6q21.
  
  The Psrs1 locus confers a high incidence of psoriasis (>87.5% at 16 weeks of age) and arthritis (>75% at 16 weeks of age) in congenic animals. The psoriasis phenotype is progressive and includes severe erythema, scale and crust formation onthe back skin, hyperplasia ofthe epidermis, hyperorthokeratosis, subcorneal microabscesses and diffuse inflammatory cell infiltration in the dermis with increased numbers of CD4+ cells, macrophages. Skin sections stained strongly for TNF-alpha. In addition, congenic animals displayed arthritic joint swelling, erythema and cartilage damage of the ankle joints and tarsometatarsal and metatarsophalangeal paw joints.
  
  Psrs3 (psoriasis susceptibility 3) is associated with earlier psoriasis onset. Interestingly, congenic animals carryingPL/J-derived DNA from D6Mit274 (20.5 cM) to D6Mit14 (71.2 cM), which includes the Psrs3 locus, on a C57BL/6J-Itgb2^tm1Bay genetic background do not develop psoriasis or arthritis by 16 weeks of age. Apparently, Psrs3 is notsufficient on its own to promote psoriasis and/or arthritis on a C57BL/6J-Itgb2^tm1Bay resistant background.