Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  13
• Reference
  J:145049 Rankin J, et al., The Bxs6 locus of BXSB mice is sufficient for high-level expression of gp70 and the production of gp70 immune complexes. J Immunol. 2007 Apr 1;178(7):4395-401
• ID
  MGI:3836726

Genes

Gene	Assay Type
Bxs6	visible phenotype
D13Mit3	PCR amplified length variant
D13Mit78	PCR amplified length variant
D13Mit253	PCR amplified length variant

Notes

• Experiment
  Congenic line analysis was used to confirm and refine previously mapped QTL Bxs6 (BXSB/MpJ autoimmune nephritis 6) on mouse Chromosome 13 near D13Mit253 (37 cM). BXSB/MpJ-derived DNA from D13Mit3 (10 cM) to D13Mit78 (75 cM) was introgressed onto a C57BL/10Ola genetic background. This congenic encompasses the Bxs6 locus and is designated B10.BXSB-(D13Mit3-D13Mit78). Parental strain BXSB/MpJ displays increased gp70 autoantibody titers and susceptibility to autoimmune nephritis whereas parental strain C57BL/10Ola is resistant. A second congenic line carrying BXSB/MpJ-derived DNA from D13Mit122 (36 cM) to D13Mit233 (45 cM) on a C57BL/10Ola genetic background was also constructed. This congenic line, designated B10.BXSB-(D13Mit122-D13Mit233) is phenotypicallyidentical to that of the first congenic line B10.BXSB-(D13Mit3-D13Mit78). Authors state data for B10.BXSB-(D13Mit3-D13Mit78) was presented for their publication. Congenic animals were also bred to carry the Y chromosome autoimmune susceptibility locus Yaa(accelerated autoimmunity and lymphoproliferation transposition). The derivative congenic line is designated B10.BXSB-(D13Mit3-D13Mit78) Yaa.
  
  B10.BXSB-(D13Mit3-D13Mit78) animals displayed significantly increased gp70 antibody titers and significantly increased levels of gp70 immune complex formation compared to animals from background strain C57BL/10Ola. B10.BXSB-(D13Mit3-D13Mit78) Yaa animals displayed greater gp70 titers, increased gp70 immune complex levels, increased nephritis incidence and severity, splenomegaly and decreased survival compared to B10.BXSB-Yaa animals. These findings suggest the Bxs6 locus confers nephritis susceptibility and the Yaa locus enhances nephritis phenotypes. The gp70 titers and gp70 immune complex levels were significantly lower in female animals compared to males of both congenic lines. Authors hypothesize a second locus may be present within the Bxs6 interval that influences gp70 immune complex formation.
  
  The Bxs6 locus does not show significant association to antinuclear antibody production, however a trend was observed toward increased anti-ssDNA and anti-dsDNA antibody titers in B10.BXSB-(D13Mit3-D13Mit78) Yaa animals compared to B10.BXSB-Yaa animals. B10.BXSB-(D13Mit3-D13Mit78) animals also displayed a trend towards increased antinuclear antibody levels compared to C57BL/10Ola inbred animals.
  
  Fine map analysis using a population of BXSB/MpJ x (C57BL/10Ola x BXSB/MpJ)F1 backcross animals refined the Bxs6 locus to a 18.9 Mb interval between 59.7 Mb and 78.6 Mb. Further refinement of Bxs6 was employed by comparing SNPs between BXSB/MpJ and a closely related strain BXSB/MpJScr-ll. A 15.1 Mb region between 59.7 Mb (D13Mit186) and 74.8 Mb (D13Mit98) is deemed the most likely location of Bxs6although the region between 78 Mb and 78.6 Mb cannot be excluded at this time. Sgp3 (37.5 cM) and Gv1 (36 cM) are previously identified autoimmunity QTLs colocalizing with Bxs6.