Arvm1^MRL/MpJ
QTL Variant Detail

Summary

• QTL variant: Arvm1^MRL/MpJ
• Name: autoimmune renal vasculitis 1; MRL/MpJ
• MGI ID: MGI:2155751
• QTL: Arvm1 Location: Chr4:46332646-46332776 bp Genetic Position: Chr4, cM position of peak correlated region/allele: 24.66 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: MRL/MpJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers vasculitis susceptibility compared to C3H/HeJ. (J:63511)
• Inheritance: Other (see notes)

Notes

Arvm1 exhibits additive inheritance and interacts with Arvm2 and Lprm2.

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

J:63511

Mapping studies of previously identified QTLs associated with systemic vasculitis were extended with a large population of MRL/MpJ-Tnfrsf6^lpr x (MRL/MpJ-Tnfrsf6^lpr x C3H/HeJ-Tnfrsf6^lpr/Tnfrsf6^lpr)F1 backcross animals (n = 179) and (MRL/MpJ-Tnfrsf6^lpr x C3H/HeJ-Tnfrsf6^lpr/Tnfrsf6^lpr)F2 intercross animals (n = 266). Inbred strain MRL/MpJ-Tnfrsf6^lpr develops severe systemic vasculitis while inbred strain C3H/HeJ-Tnfrsf6^lpr/Tnfrsf6^lpr is resistant. Loci significantly associated with susceptibility to vasculitis mapped to mouse Chromosome 4 at 19.8 cM (Arvm1, LOD = 8.0 at D4Mit89) and 58 cM (Arvm2, LOD = 6.3 at D4Mit147) and to mouse Chromosome 3 at 64 cM (P = 0.00084 at D3Mit14). Arvm1 appears to be a novel locus while Arvm2 is thought tobe identical to a locus mapped by Nakatsuru in 1999,and may share overlap with previously mapped autoimmunity-related QTLs Sle2, Nba1, Lbw2, and Lmb1. The chromosome 3 locus is thought be identical to Lprm2, a locus mapped by Wang in 1997. The 3 QTLs appear to interact in an additive fashion: animals withgenotype MRL/MRL at Arvm1, MRL/MRL at Arvm2, and MRL/C3H at the Chromosome 3 locus develop the most severe vasculitis phenotype. Pax5 and Cd72 are possible candidate genes for Arvm1, and Csf3r and Lck are possible candidate genes for Avrm2. mRNA expression levels were similar for all 4 genes in parental strains, however multiple mutations were found in the Cd72 coding region of the MRL allele.

References

• Original: J:63511 Qu WM, et al., Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72c allele. Eur J Immunol. 2000 Jul;30(7):2027-37
• All: 1 reference(s)