Faculty Research 1990 - 1999
Genetic analysis of susceptibility to dextran sulfate sodium-induced colitis in mice.
Document Type
Article
Publication Date
1999
Keywords
Animal, Chromosome-Mapping, Chromosomes, Colitis, Crosses-Genetic Dextran-Sulfate, Genetic-Markers, Genetic-Predisposition-to-Disease Linkage-Genetics, Mice, Mice-Inbred-C3H, Mice-Inbred-C57BL, Mice-Inbred-NOD, Phenotype, Quantitative-Trait, Variation-Genetics
First Page
147
Last Page
156
JAX Source
Genomics 1999 Jan 15;55(2):147-56
Grant
DK44240/DK/NIDDK, CA34196/CA/NCI
Abstract
The genetic basis for differential sensitivity of inbred mice to inflammatory bowel disease induced by dextran sulfate sodium (DSS) is unknown. Susceptible C3H/HeJ were outcrossed to partially resistant C57BL/6J mice. F2 and N2 progeny were phenotyped by evaluating histopathologic lesions in large intestine detected 16 days after a 5-day period of feeding 3.5% DSS. Screening for DSS colitis (Dssc) loci revealed quantitative trait loci (QTL) on Chr 5 (Dssc1) and Chr 2 (Dssc2). These traits contributed additively, explaining 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 lesions were indicated. In the cecum, only a putative QTL on Chr 11 was associated with pathology (lesion severity) in the cecum. Reduced DSS susceptibility 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 genes control susceptibility to DSS colitis in mice. Possible Dssc candidate genes are discussed in terms of current knowledge of inflammatory bowel disease susceptibility loci in humans. Copyright 1999 Academic Press.
Recommended Citation
Mahler M,
Bristol IJ,
Sundberg JP,
Churchill GA,
Birkenmeier EH,
Elson CO,
Leiter EH.
Genetic analysis of susceptibility to dextran sulfate sodium-induced colitis in mice. Genomics 1999 Jan 15;55(2):147-56