Genetic Dissection of Granulomatous Enterocolitis and Arthritis in the Intramural Peptidoglycan-Polysaccharide-Treated Rat Model of IBD

被引：6

作者：

Bleich, A. ^{[1
,2
]}

Hopf, S. ^{[1
,2
]}

Hedrich, H. J. ^{[1
,2
]}

van Lith, H. A. ^{[3
,4
]}

Li, F. ^{[5
]}

Sartor, R. Balfour ^{[5
]}

Maehler, M. ^{[1
,2
]}

机构：

[1] Hannover Med Sch, Inst Lab Anim Sci, D-30625 Hannover, Germany

[2] Hannover Med Sch, Cent Anim Facil, D-30625 Hannover, Germany

[3] Univ Utrecht, Fac Vet Med, Dept Anim Sci & Soc, Div Lab Anim Sci, Utrecht, Netherlands

[4] Univ Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

[5] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA

来源：

INFLAMMATORY BOWEL DISEASES | 2009年 / 15卷 / 12期

关键词：

animal models; IBD; arthritis; extraintestinal manifestation; genetics; mucosal immunology; pathology; quantitative trait; INFLAMMATORY-BOWEL-DISEASE; RHEUMATOID-ARTHRITIS; BONE LOSS; EXPRESSION; LOCUS; SUSCEPTIBILITY; PATHOGENESIS; MECHANISMS; SYSTEM; MANIFESTATIONS;

D O I：

10.1002/ibd.21018

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 clays 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 focus (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.

引用

页码：1794 / 1802

页数：9

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