Nba10^NZB
QTL Variant Detail

Summary

• QTL variant: Nba10^NZB
• Name: New Zealand Black autoimmunity 10; NZB
• MGI ID: MGI:3529870
• QTL: Nba10 Location: Chr1:152794822-186438620 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: NZB

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased susceptibility to autoimmunity compared to C57BL/6. (J:95829)
• Inheritance: Not Specified

Notes

This allele shows linkage to increased anti-chromatin and anti-DNA antibodies, increased serum gp70 immune complex levels, and severe glomerulonephritis.

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

J:95829

Linkage analysis was performed on 154 male animals from a C57BL/6 x (NZB x C57BL/6-Yaa)F1 backcross to map QTLs associated with autoimmune traits, such as anti-DNA and anti-chromatin antibody production. Parental strain C57BL/6 does not develop spontaneous autoimmune traits whereas the parental hybrid (NZB x C57BL/6-Yaa)F1 develops lupus-like nephritis and increased serum IgG anti-DNA antibodies and gp70-anti-gp70 immune complex. 95 microsatellite markers were used for the genome scan.

An interval from90 cM - 98 cM on mouse Chromosome 1 that overlapped with the previously identified Nba2 QTL showed linkage to anti-DNA (LOD=7.08) and anti-chromatin antibodies (LOD=13.24). Peak linkage occurred near Fcgr2b (92.3 cM). The NZB-derived allele confers susceptibility to autoimmunity at this locus. This locus also shows linkage to gp70 immune complex levels (LOD=7.28). Markers D1Mit36 and Fcgr2b in the region also show linkage to glomerulonephritis. Heterozygous animals exhibit more severe glomerulonephritisthan C57BL/6 homozygous animals. Male congenic animals carrying an NZB-derived locus (from D1Mit47 - D1Mit461) on a C57BL/6-Yaa genetic background exhibit increased anti-DNA, anti-chromatin antibodies, and gp70 immune complex levels and severe glomerulonephritis (50% mortality rate at 14 months of age) compared to control male C57BL/6-Yaa animals. Potential candidate genes are Fcgr2b (92.3 cM) and Ifi202a (95.3 cM).

07.16.2015. Curators Note: Because Nba2 was orginally mapped in J:23719 in 1995 using 90 female (NZB x SM/J)F1 x NZW backcross mice, which differ from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Nba10 .

The H2 locus at 23 cM on mouse Chromosome 17 showed linkage to anti-DNA (LOD=10.55) and anti-chromatin antibodies(3.02). The C57BL/6-derived allele confers susceptibility to autoimmunity at this locus. This locus is also linked to serum gp70 immune complex levels (LOD=8.9).

A locus on mouse Chromosome 13 named Sgp3 showed linkagetoserum gp70 production with peak linkage occurring near D13Mit193 (43 cM; LOD=8.77). Sgp3 is also strongly linked to gp70 immune complex levels (LOD=8.27). Markers D13Mit250 and D13Mit122 in the Sgp3 region also show linkage to glomerulonephritis. Animalsheterozygous at Sgp3 exhibit more severe glomerulonephritis than C57BL/6 homozygous animals. Male congenic animals carrying an NZB-derived Sgp3 locus (from D13Mit250 - D13Mit73) on a C57BL/6-Yaa genetic background exhibit increased serum gp70 levels compared to control male C57BL/6-Yaa animals. A potential candidate gene for Sgp3 is Gv1 at 36 cM.

10.8.2015 Curator Note: Because Sgp3 was originally mapped in J:85646 in 2003 using congenic strains, B6.NZW-Sgp3/1, -Sgp3/2 and -Sgp3/3,, which differ from the cross used here, we consider the current study a separate mapping experiment and have named this QTL (mapping to Chr 13, 43 cM; LOD=8.77) Sgp5 .

A novel locus showing association to gp70 immune complex levels named Nba5 mapped to 23 cM on mouse Chromosome 7 near D7Nds5 (LOD=4.65). Male congenic animalscarrying an NZB-derived Nba5 locus (from D7Mit154 - D7Mit194) on a C57BL/6-Yaa genetic background exhibit increased serum gp70 immune complex levels. Congenic males also exhibit some increase in severeglomerulonephritis (1/3 mortality rate at 14 monthsof age) compared to control maleC57BL/6-Yaa animals.

References

• Original: J:95829 Kikuchi S, et al., Differential role of three major New Zealand black-derived loci linked with Yaa-induced murine lupus nephritis. J Immunol. 2005 Jan 15;174(2):1111-7
• All: 7 reference(s)