Mapping Data

Experiment

• Experiment
  TEXT
• Chromosome
  Y
• Reference
  J:137656 Santiago-Raber ML, et al., Evidence for genes in addition to Tlr7 in the Yaa translocation linked with acceleration of systemic lupus erythematosus. J Immunol. 2008 Jul 15;181(2):1556-62
• ID
  MGI:3804684

Genes

Gene	Assay Type
Yaa	resistance/susceptibility

Notes

• Experiment
  The NZB-derived allele of Nba2 on mouse Chromosome 1 confers susceptibility to systemic lupus erythematosus (SLE) on a C57BL/6 genetic background and the additional presence of Yaa, a translocation of telomeric X chromosome genes onto the Y chromosome, accelerates the phenotype. Authors hypothesized duplication of the translocated X chromosome gene Tlr7 plays a role enhancing SLE susceptibility in Yaa-bearing males. Therefore, a congenic line with an X chromosome knockout allele of Tlr7 and simultaneously carrying Nba2^NZB and Yaa on a C57BL/6 genetic background was constructed (C57BL/6-Nba2^NZB Tlr7^tm1Aki Yaa). Males from this congenic line were compared to wild type males and C57BL/6-Nba2^NZB Yaa males.
  
  C57BL/6-Nba2^NZB Tlr7^tm1Aki Yaa males display reduced production of anti-dsDNA and anti-ribonucleoprotein (RNP) autoantibodies compared to C57BL/6-Nba2^NZB Yaa males. However, the presence of one copy of Tlr7 (in C57BL/6-Nba2^NZB Tlr7^tm1Aki Yaa males) did not suppress production of anti-chromatin autoantibodies or the formation of anti-gp70 immune complexes compared to the presence of two copies of Tlr7 (in C57BL/6-Nba2^NZB Yaa males).
  
  C57BL/6-Nba2^NZB Tlr7^tm1Aki Yaa males displayed increased resistance to lethal lupus nephritis witha 25% incidence of disease at 14 months of age and lower glomerulonephritis scores compared to C57BL/6-Nba2^NZB Yaa males. Authors conclude the gene duplication of Tlr7 in Yaa-bearing males significantly contributes to, but does not completely account for, the development of glomerulonephritis.
  
  Increased incidence of monocytosis (71%) was observed in C57BL/6-Nba2^NZB Yaa males at 8 months of age compared to 20% incidence of monocytosis observed in C57BL/6-Nba2^NZB Tlr7^tm1Aki Yaa males. This findingsuggests a duplication of Tlr7 in Yaa-bearing males confers increased susceptibility to monocytosis.
  
  Increased susceptibility to lethal nephritic disease in C57BL/6-Nba2^NZB Tlr7^tm1Aki Yaa males compared to wild type males suggests that other genes in the Yaa locus may modify SLE susceptibility and sub-phenotypes. One such gene in the Yaa locus is Tlr8. Further investigation is warranted to discern the influences ofTlr7, Tlr8 and other Yaa region genes on SLE susceptibility.