Genetic analysis of susceptibility to dextran sulfate sodium-induced colitis in mice

The genetic basis for differential sensitivity of inbred mice to inflammato ry bowel disease induced by dextran sulfate sodium (DSS) is unknown. Suscep tible C3H/ReJ were outcrossed to partially resistant C57BL/6J mice. F2 and N2 progeny were phenotyped by evaluating histopathologic lesions in large i ntestine detected 16 days after a 5-day period of feeding 3.5% DSS. Screeni ng for DSS colitis (Dssc) loci revealed quantitative trait loci (QTL) on Ch r 5 (Dssc1) and Chr 2 (Dssc2). These traits contributed additively, explain ing 17.5% of the variation in total colonic lesions. Additional QTL on Chr 18 and 1 that collectively explained 11% of the variation in total colon le sions were indicated. In the cecum, only a putative QTL on Chr 11 was assoc iated with pathology (lesion severity) in the cecum. Reduced DSS susceptibi lity was observed in congenic stocks in which the highly susceptible NOD/Lt strain carried putative resistance alleles from either B6 on Chr 2 or from the highly resistant NON/Lt strain on Chr 9. We conclude that multiple gen es control susceptibility to DSS colitis in mice. Possible Dssc candidate g enes are discussed in terms of current knowledge of inflammatory bowel dise ase susceptibility loci in humans. (C) 1999 Academic Press.