Elsgp4^NZB/BlNJ
QTL Variant Detail

Summary

• QTL variant: Elsgp4^NZB/BlNJ
• Name: elevated serum gp70 4; NZB/BlNJ
• MGI ID: MGI:3040486
• QTL: Elsgp4 Location: unknown Genetic Position: Chr12, cM position of peak correlated region/allele: 8.49 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: NZB/BlNJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers elevated serum gp70 levels compared to C57BL/6J. (J:89134)
• Inheritance: Recessive

Notes

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

J:89134

Linkage analysis at a resolution of 20 cM was performed using two different mouse crosses to identify QTLs associated with serum gp70 levels.

The first cross involved 222 female (NZB/BlNJ x BALB/cByJ)F2 intercross animals and the second cross involved 126 female (NZW/LacJ x BALB/c-H2^z)F1 x NZB/BINJ backcross animals. Parental strains NZB/BlNJ and NZW/LacJ are prone to lupus and produce high levels of endogenous gp70 compared to parental strain BALB/cByJ.

In the (NZB/BlNJ x BALB/cByJ)F2 intercross significant linkage was detected on mouse Chromosome 12 between 7.0-7.2cM near marker D12Mit12 (LOD=22.7). The NZB allele conferred increased serum gp70 levels and exhibited a recessive inheritance pattern. This locus is designated Elsgp4.

In the (NZW/LacJx BALB/c-H2^z)F1 x NZB/BINJ backcross significant linkage of serum pg70 levels was also detected on Chromosome 12 at 1.0cM near D12Mit291 (LOD=10.5). The NZW allele conferred the increased serum levels.

06.17.2015. The authors also refer to the locus mapped to Chromosome 12 here in the second cross as Elspq4. However, we regard the second cross, using differing strains than the first, as a separate map study and have named the QTL Elsgp7.

Elsgp7 was further confirmed by construction of a congenic linecarrying a 34 cM region of proximal chromosome 12 derived from NZW/LacJ on a BALB/cByJ background. The serum gp70 level of the congenic line was significantly elevated compared to background strain BALB/cByJ. However, serum gp70IC was not significantly elevated compared to BALB/cByJ. No candidate genes have yet been found for Elsgp7.

In the (NZB/BlNJ x BALB/cByJ)F2 intercross significant linkage was detected on mouse Chromosome 4 between 71.8-72.9 cM near marker Fv1 (LOD=5.4) The gp70 modifying allele was conferred from the NZB strain.

06.17.2015 Curator Note: This QTL on Chr 4 is referred to as Elspg1. However, Elspg1 was originally mapped in J:63674 using (NZB/BlNJ x C57BL/6J)F2 mice which differ from the strains used here. We consider this a separatemap study and have named the QTL Elsgp5.

An attractive candidate gene for Elsgp5 is Fv1(76.5 cM). The Fv1 sequence shows differences between the autoimmune (NZB/BlNJ, NZW/LacJ, BXSB) and non-autoimmune strains (BALB/cByJ, C57BL/10). In addition, interval mapping shows that Fv1 segregates with serum gp70 levels in the F2 cross.

In the (NZW/LacJ x BALB/c-H2^z)F1 x NZB/BINJ backcross suggestive linkage was also detected on Chromosome 4 near D4Mit343 (79 cM) (LOD=1.3). The gp70 modifiying allele was derived from the NZW strain. This QTL was also referred to as Elspq1 in the text. We have named this QTL Elspq6 since Elspq1 was originally mapped using (NZB/BlNJ x C57BL/6J)F2 mice.

References

• Original: J:89134 Rigby RJ, et al., A novel locus regulates both retroviral glycoprotein 70 and anti-glycoprotein 70 antibody production in New Zealand mice when crossed with BALB/c. J Immunol. 2004 Apr 15;172(8):5078-85
• All: 1 reference(s)