Lbw8^NZB/BlScr
QTL Variant Detail

Summary

• QTL variant: Lbw8^NZB/BlScr
• Name: lupus NZB x NZW 8; NZB/BlScr
• MGI ID: MGI:3033087
• QTL: Lbw8 Location: Chr11:53503287-53509492 bp Genetic Position: Chr11, Syntenic

Variant origin

• Strain of Specimen: NZB/BlScr

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers lupus suceptibility compared to NZW/LacScr. (J:20991)
• Inheritance: Dominant

Notes

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

J:20991

91 microsatellite markers were screened in a (NZB/BlScr x NZW/LacScr)F2 intercross population to identify QTLs associated with lupus susceptibility and lupus phenotypes. (NZB/BlScr x NZW/LacScr)F1 animals exhibit high susceptibility to systemic lupus erythematous (SLE) with 80% mortality by 12 months of age whereas parental strains NZB/BlScr and NZW/LacScr exhibit 16% and 11% mortality, respectively. Lupus-associated loci were detected on several chromosomes.

Lbw1 maps to 19.06 cM on mouse Chromosome 17 with marker Tnf (P<0.01) in association with mortality and glomerulonephritis.

Lbw2 maps to 55.6 cM on mouse Chromosome 4 with marker D4Nds2 (P<<0.001) in association with mortality and glomerulonephritis with NZB/BlScr-derived alleles conferring dominant lupus susceptibility at this locus. Given the early mortality for mice carrying the NZB Lbw2 allele attempts were made to more precisely map it. Based on 10 informative crossover events Lbw2 was mapped to a 9 cM span between D4Mit16 and D4Mit28.

Lbw3 maps to 81 cM on mouse Chromosome 5 with marker D5Mit101 (P<0.001) in association with mortality. NZW/LacScr-derived alleles confer recessive lupus susceptibility at Lbw3.

Lbw4 maps to 65 cM on mouse Chromosome 6 with marker D6Mit25 (P<<0.001) in association with mortality. NZB/BlScr-derived alleles confer recessive lupus susceptibility at Lbw4.

Lbw5 maps to 23 cM on mouse Chromosome 7 with marker Ngfg (P<0.01) in association with mortality with NZW/LacScr-derived alleles conferring dominant lupus susceptibility at this locus.

Lbw6 maps to 47 cM on mouse Chromosome 18 with marker D18Mit8 (P<0.005) in association with mortality and glomerulonephritis. NZW/LacScr-derived alleles confer recessive lupus susceptibility at Lbw6.

Lbw7 maps to 92.3 cM on mouse Chromosome 1 with marker D1Mit36 (P<0.005) and

Lbw8 maps to 29 cM on mouse Chromosome 11 with marker Il4 (P<0.005) in association with anti-chromatin antibody production. NZB/BlScr-derived alleles confer dominant lupus susceptibility at Lbw7 and Lbw8.

Two loci associated with splenomegaly, Sbw1 and Sbw2, were detected on mouse Chromosome 1 at 66.8 cM (P<0.005 at D1Nds1) and mouse Chromosome 4 at 44.5 cM (P<<0.001 at D4Mit9), respectively. Sbw2 was furtherlocalized to a 7 cM region between markers D4Mit16 and D4Nds2. Authors state that Sbw2 and Lbw2 map to the same region on mouse Chromosome 4 and are likely to be the same susceptibility locus.

NZB/BlScr-derived alleles confer recessive splenomegaly susceptibility at Sbw1 and dominant splenomegaly susceptibility at Sbw2.

References

• Original: J:20991 Kono DH, et al., Lupus susceptibility loci in New Zealand mice. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10168-72
• All: 1 reference(s)