Lxw4^NZW/LacScr
QTL Variant Detail

Summary

• QTL variant: Lxw4^NZW/LacScr
• Name: lupus BXSB x NZW 4; NZW/LacScr
• MGI ID: MGI:3036330
• QTL: Lxw4 Location: Chr5:52694462-52694594 bp Genetic Position: Chr5, cM position of peak correlated region/allele: 28.24 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: NZW/LacScr

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased survival time compared to BXSB/Scr. (J:86924)
• Inheritance: Not Specified

Notes

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

J:86924

Genome scan was performed on a population of female (BXSB/Scr x NZW/LacScr)F2 animals to identify QTLs associated with autoimmune lupus susceptibility traits. 132 polymorphic loci were examined. Parental strain NZW/LacScr exhibits greater susceptibility for lupus-associated traits (such as glomerulonephritis (GN), degenerative vascular disease (DVD), myocardial infarction (MI), arteritis, and decreased survival time.

Lxw1 (lupus BSXB x NZW 1) mapped to 6.5 cM on mouse Chromosome 4 in linkage to early anti-chromatin antibody production at 6 months (P=0.0002 at D4Mit2.) BXSB/Scr-derived alleles confer susceptibility at Lxw1 (increased anti-chromatin antibody production). Lxw1 accounts for 13% of the phenotypic variance.

Lxw2 mapped to 25.5 cM on mouse Chromosome 6 in linkage to glomerulonephritis (P=0.004 at D6Mit33). NZW/LacScr-derived alleles confer increased susceptibility at Lxw2 (increased glomerulonephritis) with a recessive mode of inheritance. Lxw2 accounts for 16% of the phenotypic variance.

Lxw3 mapped to 63.8 cM on mouse Chromosome 1 in linkage to late anti-chromatin antibody production at 10-11 months (P=4.2 x 10-4 at D1Mit54). NZW/LacScr-derived alleles confer susceptibility at Lxw3 (increased anti-chromatin antibody production). Lxw3 also shows suggestive linkage to arteritis.

Lxw4 mapped to 28 cM on mouse Chromosome 5 in linkage to survival (P<0.007 at D5Mit55). NZW/LacScr-derived alleles confer increased susceptibility (decreased survival time). Authors note this locus overlaps and may be identical to a previously identified QTL named Sle6.

Lxw5 mapped to 43.1 cM on mouse Chromosome 1 in linkage to splenomegaly (P=0.03 at D1Mit46). BXSB/Scr-derived alleles confer susceptibility (increased splenomegaly) with an additive mode of inheritance. This locus accounts for 19% of the phenotypic variance. Lxw5 colocalizes with previously mapped QTLs Yaa2, Yaa3, Sle7, and Sle8. Authors note Lxw5 may represent an identical locus.

Lxw6 mapped to 1 cM on mouse Chromosome 7 in linkage to splenomegaly (P=5.5 x 10-3 at D7Mit152). NZW/LacScr-derived alleles confer susceptibility (increased splenomegaly) with a recessive mode of inheritance at Lxw6. This locus accounts for 15.5% of the phenotypic variance. Authors note Lxw6 maps near previously identified QTLs Lbw5 and Sle3 and may be identical.

The H2 locus on mouse Chromosome 17 was associated with several lupus phenotypes such as survival, anti-chromatin antibody production, glomerulonephritis, splenomegaly, and arteritis. The BXSB/Scr-derived allele at this locus confers increased anti-chromatin Ab production (P=5.1 x 10-6), severe glomerulonephritis (P=4.3 x 10-5), and splenomegaly (P=1.1 x 10-3). Heterozygosity at this locus appears to confer decreased survival time (P<0.0016).

Suggestive linkage to arteritis was detected at 61 cM (D6Mit256) on mouse Chromosome 6 and at 47.4 cM (D17Mit256) on mouse Chromosome 17. The NZW/LacScr-derived allele confers susceptibility at chromosome 6 while the BXSB/Scr-derived allele confers susceptibility at chromosome 17.

References

• Original: J:86924 Kono DH, et al., Genetic complementation in female (BXSB x NZW)F2 mice. J Immunol. 2003 Dec 15;171(12):6442-7
• All: 1 reference(s)