Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  2
• Reference
  J:171572 Esworthy RS, et al., Colitis locus on chromosome 2 impacting the severity of early-onset disease in mice deficient in GPX1 and GPX2. Inflamm Bowel Dis. 2011 Jun;17(6):1373-86
• ID
  MGI:5810640

Genes

Gene	Assay Type
Gdac1	visible phenotype

Notes

• Experiment
  Identification of susceptibility genes has become a major goal for IBD (inflammatory bowel disease) research. Gpx1 and Gpx2 double knockout (GPX1/2-DKO) mice on a mixed C57BL/6J (B6) and 129S1/SvImJ (129) have spontaneous ileocolitis. DKO mice on a B6 Background have mild ileocoloitis.
  
  Gpx1 and Gpx2 double knockout mice (GPX1/2-DKO, homozygous for Gpx1^tm1Ysh and Gpx2^tm2Coh) on a mixed C57BL/6J (B6) and 129S1/SvImJ (129) background (F1 hybrid and N5-N10 on 129) have spontaneous ileocolitis. DKO mice on a B6 background (N8) have mild colitis.
  
  In this study 129 DKO mice were characterized to identify QTL affecting disease severity. B6;129 DKO mice were backcrossed to 129 mice and analyzed for ileocolitis penetrance and severity in N5, N7 and N10. By correlating severity of disease with single nucleotide polymorphism (SNP) markers, a colitis locus was identified
  
  GPX1/2 DKO mice were generated by mating Gpx1^{tm1Ysh/tm1Ysh} (Gpx1-KO) and Gpx2^{tm2Coh/tm2Coh} (Gpx2-KO) mice. The GPX1/2-DKO colony on a mixed B6;129 strain background was backcrossed to C57BL/6J to generate B6 (N8) and to 129S1/SvimJ to generate 129 N5, N7, and N10 colonies.
  
  Disease onset, survival time, differences in colon pathology scores, mouse health and weight, and general absence of disease signs were analyzed. For QTL analysis R/QTL was used with the J/QTL interface. The physical positions of markers were translated to cM using nearby mapped genome features.
  
  GPX1/2 DKO mice on a 129 genetic background had the most aggressive colitis compared with B6;129 and B6 mice. Analysis of the B6 loci in 129 N5, N7 and N10 mice pointed to a region of Chromosome 2 contributing to mild symptoms.
  
  An analysis of colon histopathology of DKO 129 N10, 129 N5-N7 and B6 mice suggested that stratification of alleles at 119 Mbp (129/129 vs B6/129 vs B6/B6) accounted for a large portion of the variation in colon histopathology scores between B6 and 129 strains with additive inheritance. Running the combined N5-N7 data set in R/QTL using colon scores gave similar results to the analysis based on mouse health and body weight for N5-N7.
  Chromosome 2:125-126 Mbp (119-130 Mbp; Bayesian credible interval, 0.95) was identified with a peak LOD score of 6.35-7.01. The QTL was labeled Gdac1, glutathione peroxidase deficiency associated colitis 1. The interval accounted for 34%, 37.5%, and 27% of the variation in proximal, distal, and composite scores, respectively.
  
  Gdac1 mapped in the vicinity of QTL Cdcs3 (cytokine deficiency colitis susceptibility 3).
  Among 36 genes exhibiting non synonymous coding SNPs in the region of Chr 2:118-130 Mbp, B2m, Dnajc17, Duox2, Pla2g4b, Pla2g4f and Scl30a4 stand out as plausible candidates for colitogenic genes based on the assumption of replication.