Ibdq2^AKR/J
QTL Variant Detail

Summary

• QTL variant: Ibdq2^AKR/J
• Name: inflammatory bowel disease QTL 2; AKR/J
• MGI ID: MGI:3655691
• QTL: Ibdq2 Location: Chr6:105982366-120894102 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: AKR/J

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:105411

Linkage disequilibrium analysis was performed on 89 (AKR/J x SAMP1/YitFcs)F1 x SAMP1/YitFcs backcross animals to identify loci associated with susceptibility to inflammatory bowel disease. A panel of 43 polymorphic markers was used for the analysis. Parental strain SAMP1/YitFcs is susceptible to inflammatory bowel disease and develops ileitis beginning at 10 weeks of age. Parental strain AKR/J is resistant and exhibits low inflammatory scores even at 30 weeks of age.

Ibdq2 (inflammatory bowel disease QTL 2) mapped to 51 cM (118.2 Mb) on mouse Chromosome 6 near D6Mit288 (LRS=15.3; p=0.0001). This locus reached suggestive significance in a previous study identifying Ibdq1 (J:84661). SAMP1/YitFcs-derived alleles at Ibdq2 confer ileitis susceptibility with a recessive mode of inheritance. The Ibdq2 QTL interval spans D6Mit149 (43.6 cM; 106.8 Mb) to Bid (54 cM; 121.7 Mb). Several potential candidate genes are found in this region including Tnfrsf1a (60.55 cM), Cd4 (60.18 cM), and Ltbr (60.4 cM). A particularly strong candidate gene is Pparg (52.7 cM). SAMP1/YitFcs animals exhibit decreased Pparg in the ileum and jejunum compared to AKR/J animals. Treatment of 30 week old (C57BL/6J x SAMP1/YitFcs)F1 animals exhibiting ileitis with a Pparg agonist (rosiglitazone) decreased inflammation scores by 25%-50%. Interestingly, treatment of SAMP1/YitFcs parental animals did not have the same effect. In addition, PPARG (3p25-p26) has been linked to Crohn's disease in humans.

References

• Original: J:105411 Sugawara K, et al., Linkage to peroxisome proliferator-activated receptor-gamma in SAMP1/YitFc mice and in human Crohn's disease. Gastroenterology. 2005 Feb;128(2):351-60
• All: 1 reference(s)