Lprm2^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Lprm2^C3H/HeJ
• Name: lymphoproliferation modifier 2; C3H/HeJ
• MGI ID: MGI:2155324
• QTL: Lprm2 Location: Chr3:136778857-136779044 bp Genetic Position: Chr3, cM position of peak correlated region/allele: 63.44 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers vasculitis susceptibility in female animals compared to MRL/MpJ.
• Inheritance: Dominant

Notes

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

J:44625

82 MRL/MpJ-Tnfrsf6^lpr x (MRL/MpJ-Tnfrsf6^lpr x C3.MRL-Tnfrsf6^lpr)F1 backcross animals were used to identify QTLs modifying the lpr (lymphoproliferation) mutant phenotype. Genotyping was performed with 76 microsatellite markers covering 84% of the mouse genome at an average spacing of 20 cM. The MRL/MpJ-Tnfrsf6^lpr parental strain is susceptible to developing glomerulonephritis (98.2%) and vasculitis (86%) whereas the C3.MRL-Tnfrsf6^lpr strain is resistant (0%) for both phenotypes. (MRL/MpJ-Tnfrsf6^lpr x C3.MRL-Tnfrsf6^lpr)F1 animals are resistant to glomerulonephritis (3%) and vasculitis (18%) development. Both strains exhibit lymph node swelling and splenomegaly in varying degrees. A QTL associated with vasculitis susceptibility, Lprm1 (P = 0.0009 at D4Mit178; 35.5 cM), maps to mouse chromosome 4 from 34 cM - 36 cM. MRL/MpJ-Tnfrsf6^lpr-derived alleles contribute recessively inherited susceptibility to vasculitis at this locus. However, MRL/MpJ-Tnfrsf6^lpr-derived alleles at Lprm2 (P = 0.0001 at D3Mit16; 66.2 cM), a QTL mapping to mouse chromosome 3 from 64 cM - 66 cM, confers female-specific recessively inherited vasculitis resistance. A possible candidate gene for Lprm1 is Tlr4 (the lps gene) at 33 cM. Lprm1 also maps near Nba1 (Drake, J:23719) and Sle2 (Morel, J:25006). Lprm3 (P = 0.0004 at D14Mit195; 44.3 cM), a QTL associated with glomerulonephritis resistance, maps to mouse chromosome 14 from 30 cM - 63 cM. MRL/MpJ-Tnfrsf6^lpr-derived alleles at this locus confer recessively inherited glomerulonephritis resistance. Lprm4 (P = 0.0006 at D5Mit23; 54 cM) is associated with susceptibility to splenomegaly and maps to mouse chromosome 5 from 41 cM - 54 cM. MRL/MpJ-Tnfrsf6^lpr-derived alleles at this locus confer recessively inherited splenomegaly susceptibility. Lprm5 (P = 0.0001 at D16Mit3; 21 cM) is associated with anti-dsDNA antibody titer and maps to mouse chromosome 16 from 21 cM - 38 cM. MRL/MpJ-Tnfrsf6^lpr-derived alleles at this locus confer recessively inherited high antibody titers.

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 arepossible 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)