Nba9^NZB/BlNJ
QTL Variant Detail

Summary

• QTL variant: Nba9^NZB/BlNJ
• Name: New Zealand Black autoimmunity 9; NZB/BlNJ
• MGI ID: MGI:3040475
• QTL: Nba9 Location: Chr1:172525623-172527533 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: NZB/BlNJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

The Nba9 was linked with both autoantibodies and nephritis disease but was not linked with gp70 levels in the (B6.H2 x NZB/BlNJ)F1 x NZB/BlNJ backcross. djr

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

J:40638

Authors localized the Nba2 quantitative trait locus (QTL) associated with lupus nephritis and the production of multiple autoantibody specificities implicated in the pathogenesis of the disorder. This locus was mapped with the stongest linkage to mouse Chromosome 1, using 82 (NZB/BlNJ x SM/J)F1 x NZW/LacJ. Peak linkage was observed at D1Mit48 and D1Mit111 with p^{0.002 at 92cM.}

Using 133 (B6.H2 x NZB)F1 x NZB backcross mice the authors map a QTL to a similar postion on Chromosome 1, peak linkage with Crp, p<0.001 at 94cM. A genome wide screen of the B6 backcross was completed with a total of 80 SSLP markers

07.15.2015 Curator Note: Because two different crosses were used in this study we consider each a separate mapping experiment and have named the QTL identified in the B6 cross Nba9.

When the data from both crosses was combined peak linkage was apparent between 94 and 96cM.. The 95% confidence interval is between 92 -97cM.

Both Nba2 and Nba9 were linked (or showed a trend for linkage) with elevated serum levels of multiple autoantibodies, hypergammaglobulinemia and IgG1, IgG2a and/or IgG3 levels in each backcross.

J:46190

Authors confirmed the linkage of Nba2 quantitative trait locus (QTL) on mouse Chromosome 1 with multiple IgG autoantibody levels associated with lupus nephritis in (B6.E^z x NZB/BlNJ)F1 x NZB/BlNJ backcross mice.

07.15.2015 Curator Note: Because Nba2 was originally mapped in J:23719 in 1994 using 90 female (NZB x SM/J)F1 x NZW backcross mice, which differ from the cross used here, we consider this a separate mapping experiment and have named the QTL Nba9.

J:63674

Linkage analysis was performed on 152 female (B6.H2^z x NZB/BlNJ)F1 x NZB/BlNJ backcross animals and 163 female (NZB/BlNJ x C57BL/6J)F2 intercross animals to identify QTLs linked to elevated serum gp70 (which is associated with the development of gp70 immune complexes and nephritis). 90 microsatellite markers were used in the genome scan. Parental strain NZB/BlNJ is susceptible to autoimmune nephritis compared to parental strain C57BL/6J.

In both the backcross and intercross populations two significantloci, Elsgp1 (elevated serum gp70 1) and Elsgp2, mapped to 66.6 cM on mouse Chromosome 4 (LOD=11.2 at D4Mit170) and to 40 cM on mouse Chromosome 13 (LOD=11 at D13Mit98), respectively. Elsgp2 maps near a previously identified QTL on chromosome 13 named Yaa1 (35 cM) that is also associated with serum gp70 levels. A third locus, Elsgp3, mapped to 49.6 cM on mouse Chromosome 2 (LOD=4.9 at D2Mit14). NZB/BlNJ-derived alleles confer elevated serum gp70 at all 3 loci with additive inheritance. Animals homozygousfor NZB/BlNJ-derived alleles at both Elsgp1 and Elsgp2 exhibit the highest levels of serum gp70. Elsgp1, Elsgp2, and Elsgp3 together account for 83% of the phenotypic variance in F2 mice. These loci, however, do not show linkage to gp70 immune complex levels.

In the backcross population a previously identified QTL on distal mouse Chromosome 1 named Nba2 was detected in linkage to autoantibody production and nephritis, but not to serum gp70 levels. Nba2 did not show linkage in the F2 population.

07.16.2015 Curator Note: The NZB autoimmunity locus mapped here was originally mapped to Chromosme 1 in J:40638 in 1997 using the same backcross population, (B6.H2^z x NZB/BlNJ)F1 x NZB/BlNJ. This is QTL Nba9. The F2 mice in the (NZB/BlNJ x C57BL/6J)F2 intercross showed no detectable influence on any of the traits being measure in this study.

References

• Original: J:63674 Tucker RM, et al., Genetic control of glycoprotein 70 autoantigen production and its influence on immune complex levels and nephritis in murine lupus. J Immunol. 2000 Aug 1;165(3):1665-72
• All: 1 reference(s)