Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  6
• Reference
  J:239222 Jiao Y, et al., Identifying a major locus that regulates spontaneous arthritis in IL-1ra-deficient mice and analysis of potential candidates. Genet Res (Camb). 2011 Apr;93(2):95-103
• ID
  MGI:5827925

Genes

Gene	Assay Type
Liq2	visible phenotype

Notes

• Experiment
  To better understand the pathogenesis of spontaneous arthritis in Il-1ra-defieicent mice whole genome linkage analysis was performed to detect QTL that regulate disease incidence and severity.
  
  Susceptible, IL-1ra deficient BALB/c mice, CA.129-Il1rn^tm1Yiw, were crossed with resistant DBA/1 IL-1ra-deficient mice, D1.129(CA)-Il1rn^tm1Yiw, to generate F1 mice which were then crossed to produce 600 F2 mice. Spontaneous arthritis in the F2 population was examined, scored for inflammation and recorded. The disease states of mice in the F2 population fell into all categories of disease severity from none to severe; leading to the hypothesis that there are mutliple genes that influence susceptibility to spontaneous arthritis in IL-1ra deficient mice with BALB/c alleles tending to increase susceptibility and DBA/1 alleles tending to decrease it. Male mice had a higher spontaneous arthritis incidence in all measured categories.
  
  Two cohorts of F2 populations were used in the genetic mapping. The first set, of 191 F2 mice, along with 5 mice from the two parental lines and F1 mice, were genotyped along the whole genome using 137 microsatellite markers with an average of 12 cM spacing to determine the correlation between arthritis phenotypes and genotypes. QTL Liq1 (limb inflammation 1) and Liq2 (limb inflamation QTL 2) on Chrs 1 and 6 respecitively were above the significance threshold with weaker, potential QTL mapping to Chrs 11, 12 and 14.
  
  The QTL on Chr 1 mapped between D1Mit303 and D1Mit145 with a peak at 67.4 cM between D1Mit217 and D1Mit102. A possible second peak mapped to 81.6 cM near D1Mit425.
  
  To confirm and finely map the QTL on Chr 1 an additional 561 F2 progeny were genotyped. The Chr 1 QTL mapped with a peak at 82.6 cM near D1Mit55 and D1Mit425 in a region homologous with human 1q23-25, 1q25-31,1q31 and 1q32. Liq1 may determine as much as 12% of trait susceptibility to spontaneous arthritis.
  
  The QTL region (D1Mit265-D1Mit540, ENS release 57, May 2010) contained 208 known transcripts. According to their functions, Mr1, Plag24a, and Fasl were outstanding candidate genes. From microarray analysis, 11 genes were selected as favorable candidates based on their function and expression profiles. Three of those 11 genes, Prg4, Ptgs2 and Mr1, correlated with the Il-1ra pathway.