RGD Reference Report - Genetic dissection of granulomatous enterocolitis and arthritis in the intramural peptidoglycan-polysaccharide-treated rat model of IBD. - Rat Genome Database

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

Authors: Bleich, A  Hopf, S  Hedrich, HJ  Van Lith, HA  Li, F  Balfour Sartor, R  Mahler, M 
Citation: Bleich A, etal., Inflamm Bowel Dis. 2009 Jun 12;15(12):1794-1802.
RGD ID: 2316974
Pubmed: PMID:19526527   (View Abstract at PubMed)
PMCID: PMC2889022   (View Article at PubMed Central)
DOI: DOI:10.1002/ibd.21018   (Journal Full-text)

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. Inflamm Bowel Dis 2009.

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Aia10  (Adjuvant induced arthritis QTL 10)
Aia11  (Adjuvant induced arthritis QTL 11)
Aia12  (Adjuvant induced arthritis QTL 12)
Aia13  (Adjuvant induced arthritis QTL 13)
Aia14  (Adjuvant induced arthritis QTL 14)
Aia15  (Adjuvant induced arthritis QTL 15)
Aia16  (Adjuvant induced arthritis QTL 16)
Aia17  (Adjuvant induced arthritis QTL 17)
Aia18  (Adjuvant induced arthritis QTL 18)
Aia19  (Adjuvant induced arthritis QTL 19)
Aia20  (Adjuvant induced arthritis QTL 20)
Aia21  (Adjuvant induced arthritis QTL 21)
Aia22  (Adjuvant induced arthritis QTL 22)
Aia23  (Adjuvant induced arthritis QTL 23)
Aia24  (Adjuvant induced arthritis QTL 24)
Aia25  (Adjuvant induced arthritis QTL 25)
Aia26  (Adjuvant induced arthritis QTL 26)
Aia27  (Adjuvant induced arthritis QTL 27)
Aia6  (Adjuvant induced arthritis QTL 6)
Aia7  (Adjuvant induced arthritis QTL 7)
Aia8  (Adjuvant induced arthritis QTL 8)
Aia9  (Adjuvant induced arthritis QTL 9)
Ginf1  (Gastrointestinal inflammation QTL 1)
Ginf2  (Gastrointestinal inflammation QTL 2)
Ginf3  (Gastrointestinal inflammation QTL 3)
Livw3  (Liver weight QTL 3)
Wbc3  (White blood cell count QTL 3)
Wbc4  (White blood cell count QTL 4)
Wbc5  (White blood cell count QTL 5)

F344/NCrl  (NA)
LEW/Crl  (Lewis)

Additional Information