Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  15
• Reference
  J:76107 Kamogawa J, et al., Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains. Arthritis Rheum. 2002 Apr;46(4):1067-74
• ID
  MGI:2387305

Genes

Gene	Assay Type
Paam1	resistance/susceptibility
D15Mit111
D15Mit18
Angpt1	reported elsewhere
Mapk8ip3	reported elsewhere
Ank	reported elsewhere

Notes

• Experiment
  Genome scan was performed on 179 animals from an MRL/MpJ-Tnfrsf6^lpr/Tnfrsf6^lpr x (MRL/MpJ-Tnfrsf6^lpr/Tnfrsf6^lpr x C3H/HeJ-Tnfrsf6^lpr/Tnfrsf6^lpr)F1 backcross to map QTLs associated with arthritis susceptibility. 273 polymorphic markers were employed in the linkage analysis. Parental strain MRL/MpJ-Tnfrsf6^lpr/Tnfrsf6^lpr is susceptible to arthritis compared to parental strain C3H/HeJ-Tnfrsf6^lpr/Tnfrsf6^lpr. Loci with significant linkage to progression of autoimmune arthritis, Paam1 and Paam2, mapped to mouse Chromosomes 15 and 19, respectively. Paam1 is linked to arthritis susceptibility in males with LOD=3.5 and has a QTL range of 17.8 cM - 18.7 cM on chromosome 15. MRL-derived alleles confer recessive susceptibility at Paam1. Candidate genes mapping near Paam1 are Agpt (Ang1), Mapk8ip3 (Syd2), and ank. Pgia8, a previously mapped QTL associated with proteoglycan-induced arthritis is also in the region of Paam1. Paam2 affects arthritis susceptibility in both males and females with LOD=4.3and has a QTL range of 43 cM - 55 cM on chromosome 19. MRL-derived alleles confer recessive susceptibility at Paam2. Candidate genes for Paam2 include Fgf8, Nfkb2, Col7a1, and Csf2ra. Pgia12, a previously mapped arthritis QTL, also maps near Paam2. Suggestive loci also mapped in this cross are a resistance locus near D7Mit69 (24.5 cM), a male-specific susceptibility locus near D2Mit37 (45 cM), and a susceptibility locus at D1Mit115/D1Mit358 (99.7 cM/100 cM). Loci interaction analysis revealed highly increased arthritis incidence (77.3%) in males with susceptible genotypes at Paam1 (M/M), D2Mit37 (M/M), and D7Mit69 (M/C). In addition, male animals with genotype M/M at Paam1 + M/M at D2Mit37 showed 76.9% incidence of arthritis, and male animals with genotype M/M at Paam1 and M/C at D7Mit69 showed 80 incidence of arthritis.