Paam1^MRL/MpJ
QTL Variant Detail

Summary

• QTL variant: Paam1^MRL/MpJ
• Name: progression of autoimmune arthritis in MRL mice 1; MRL/MpJ
• MGI ID: MGI:2387307
• QTL: Paam1 Location: unknown Genetic Position: Chr15, Syntenic

Variant origin

• Strain of Specimen: MRL/MpJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers arthritis susceptibility compared to C3H/HeJ. (J:76107)
• Inheritance: Recessive

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:76107

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.

References

• Original: 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
• All: 1 reference(s)