Nba5^NZB
QTL Variant Detail

Summary

• QTL variant: Nba5^NZB
• Name: New Zealand Black autoimmunity 5; NZB
• MGI ID: MGI:3529872
• QTL: Nba5 Location: unknown Genetic Position: Chr7, 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 serum gp70 immune complex levels and some linkage to 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 severe glomerulonephritis (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: 1 reference(s)