Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  15
• Reference
  J:225057 Papapietro O, et al., R-spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea. Nat Commun. 2013;4:1898
• ID
  MGI:5881906

Genes

Gene
Criq3
Rspo2

Notes

• Experiment
  The current study performed genetic, physical, bioinformatic and functional dissection of the Criq3 locus to identify pathological Rspo2-mediated Wnt activation as a major contributor to mortality following Citrobacter rodentium infection in mice. Chromosome 15 QTL have been identified as the common cause of susceptibility of the only four inbred strains (C3H/HeJ, C3H/HeOuJ, FVB/NJ, AKR/J) known to be hypersensitive to C. rodentium infection.
  
  QTL Criq3 was previously identified in J:239658 using a (C3H/HeOuJ x C57BL/6J) F2 mapping population and congenic C3Ou.B6-(rs3698904-rs3702158) mice. To test the effect of Criq3 on the B6 background a region of Chromosome 15 containing Criq3 was introgressed from the C3H/HeOuJ genome onto the resistant B6 background. 45% of the congenic animals succumbed to the infection between 13 and 28 days post infection. Despite modifying effects of the background genome the genetic origin of Criq3 is a major determinant of C. rodentium outcome.
  
  To refine the localization of the Criq3 locus two sub-congenic lines derived from resistant C3Ou.B6-(rs3698904-rs3702158) congenic mice were used. [Fig 1.a.] Mice from sub-congenic line, C3Ou.B6-(D15Mit3-rs3704632), congenic region 41.20-68.76 Mb were resistant to infection (100% survival 30 days post infection). In sub-congenic line B, C3Ou.B6-(rs3656705-rs49753698) congenic region 45.16-62.47 Mb, the introgression of segments from the resistant B6 genome had no effect on survival leading to 92% mortality of the strain 14 days post infection. The results unambiguously localize Criq3 to an ~4 Mb interval. Haplotype analysis of this region identified a common and specific haplotype block shared by susceptible mice and absent from resistant mouse strains that encompassed five genes: Rspo2, Eif3e, Gm10373, Emc2 and Tmem74.
  
  Sequence analysis of the five genes found no coding differences between the susceptible and the resistant strains. Expression analysis, determined by qPRC in colonic samples, found the Rspo2 gene to be rapidly, strongly and continuously induced during infection in susceptible C3H/HeOuJ mice where no up regulation of transcript was observed in resistant congenic mice, nor the other four candidate genes.