Nba2^NZB
QTL Variant Detail

Summary

• QTL variant: Nba2^NZB
• Name: New Zealand Black autoimmunity 2; NZB
• MGI ID: MGI:5697726
• QTL: Nba2 Location: Chr1:168835111-168835280 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: NZB

Variant description

• Allele Type: QTL

Notes

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:23719

NZB and NZW mice spontaneously develop an autoimmune process remarkably simiar to human systemic lupus erythematosus. To identify additional NZB contributors to lupus like disease 90 female (NZB x SM/J)F1 x NZW backcross mice were followed for the development of severe renal disease and were comprehensively phenotyped. To identify disease associated loci the same mice were genotyped using PCR.

A statistically significant association with disease was noted at 6 separate locations on Chrs 1, 4, 7, 10, 13 and 19. p<0.05 was the cutoff to define statistical significance. Mice carrying the NZB allele at five of these 6 positions died from severe renal disease.

Of the six significant loci evident in the backcross, the level of association with disease at the Chromosome 1 locus was particularly strong, p<0.02, peaking with marker D1Mit111 at 61cM. This QTL has been named Nba2.

The Chromosome 7 locus has been labeled Nba3, peaking with marker D7Mit17, p<0.008 at 45.0cM

References

• Original: J:23179 Behan DP, et al., Cloning and structure of the human corticotrophin releasing factor-binding protein gene (CRHBP) [published erratum appears in Genomics 1994 Jan 1;19(1):198]. Genomics. 1993 Apr;16(1):63-8
• All: 3 reference(s)