DESCRIPTION:

QTL Associated with Liver weight. On Chromosome 8 with a LOD score= 2.43, p-value =0.01. From a(n) intercross of

LABEL:

QTL-Livw3-Rat-Chr 8

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Bleich A, Hopf S, Hedrich HJ, van Lith HA, Li F, Balfour Sartor R, Mähler M

TITLE:

Genetic dissection of granulomatous enterocolitis and arthritis in the intramural peptidoglycan-polysaccharide-treated rat model of IBD.

JOURNAL:

Inflammatory bowel diseases None None, Vol 15, pp. 1794-802

ABSTRACT:

1. Inflamm Bowel Dis. 2009 Dec;15(12):1794-802. doi: 10.1002/ibd.21018. Epub 2009 Jun 12. 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. Author information: (1)Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany. bleich.andre@mh-hannover.de 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 human diseases. Copyright © 2009 Crohn's & Colitis Foundation of America, Inc. PMCID: PMC2889022 PMID: 19526527 [PubMed - indexed for MEDLINE] PUBMED: 19526527
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