1. Inflamm Bowel Dis. 2009 Dec;15(12):1794-802. doi: 10.1002/ibd.21018. Epub 2009
Genetic dissection of granulomatous enterocolitis and arthritis in the intramural
peptidoglycan-polysaccharide-treated rat model of IBD.
Bleich A(1), Hopf S, Hedrich HJ, van Lith HA, Li F, Balfour Sartor R, Mähler M.
(1)Institute for Laboratory Animal Science and Central Animal Facility, Hannover
Medical School, Hannover, Germany. email@example.com
BACKGROUND: Inflammatory arthropathies are common extraintestinal manifestations
of inflammatory bowel diseases (IBD). As genetic susceptibility plays an
important role in the etiology of IBD, we questioned how granulomatous
enterocolitis and arthritis are genetically controlled in an experimental animal
model displaying both conditions.
METHODS: Chronic intestinal and systemic inflammation was induced by intramural
injection of peptidoglycan-polysaccharide (PG-PS) polymers in the ileocecal
region of female F2 progeny derived from susceptible LEW and resistant F344 rats.
Animals were followed for 24 days after injection and phenotyped by evaluating
gross gut lesions, liver weight and granulomas, hematocrit, white blood cell
count, and change in rear ankle joint diameters. Coinheritance of the phenotypic
parameters with polymorphic DNA markers was analyzed by genome-wide quantitative
trait locus (QTL) analysis.
RESULTS: Linkage analysis revealed significant QTLs for enterocolitis and/or
related phenotypes (liver granulomas, white blood cell count) on chromosomes 8
and 17. The QTL on chromosome 8 also showed suggestive linkage to arthritis.
Significant QTLs for arthritis were detected on chromosomes 10, 13, 15, and 17.
Analyses of the modes of inheritance showed arthritogenic contributions by both
parental genomes. In addition, several other loci with suggestive evidence for
linkage to 1 or several phenotypes were found.
CONCLUSIONS: Susceptibility to PG-PS-induced chronic intestinal and systemic
inflammation in rats is under complex multigenic control in which the genetic
loci regulating arthritis are largely different from those controlling
enterocolitis. Possible candidate genes within these QTL (including
Tnfrsf11a/RANK, Gpc5, Il2ra, and Nfrkb) are also implicated in the respective
Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.
PMID: 19526527 [PubMed - indexed for MEDLINE]
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