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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ginf1RatEnterocolitis  IAGP induced by peptidoglycan-polysaccharideRGD 
Ginf2RatEnterocolitis  IAGP induced by peptidoglycan-polysaccharideRGD 
Ginf3RatEnterocolitis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia10Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia11Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia12Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia13Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia14Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia15Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia16Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia17Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia18Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia19Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia20Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia21Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia22Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia23Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia24Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia25Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia26Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia27Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia6Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia7Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia8Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia9Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Ginf1Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Ginf2Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Ginf3Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Livw3Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Wbc3Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Wbc4Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Wbc5Ratinflammatory bowel disease  IAGP induced by peptidoglycan-polysaccharideRGD 
Wbc3Ratleukopenia  IAGP induced by peptidoglycan-polysaccharideRGD 
Wbc4Ratleukopenia  IAGP induced by peptidoglycan-polysaccharideRGD 
Wbc5Ratleukopenia  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia10Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia11Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia12Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia13Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia14Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia15Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia16Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia17Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia18Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia19Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia20Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia21Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia22Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia23Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia24Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia25Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia26Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia27Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia6Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia7Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia8Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 
Aia9Ratrheumatoid arthritis  IAGP induced by peptidoglycan-polysaccharideRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Wbc3Ratdecreased leukocyte cell number  IDA induced by peptidoglycan-polysaccharideRGD 
Wbc4Ratdecreased leukocyte cell number  IDA induced by peptidoglycan-polysaccharideRGD 
Wbc5Ratdecreased leukocyte cell number  IDA induced by peptidoglycan-polysaccharideRGD 
Livw3Ratdecreased liver weight  IDA induced by peptidoglycan-polysaccharideRGD 
Ginf1Ratgranulomatous inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Ginf2Ratgranulomatous inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Ginf3Ratgranulomatous inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Ginf1Ratintestinal inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Ginf2Ratintestinal inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Ginf3Ratintestinal inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia10Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia11Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia12Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia13Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia14Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia15Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia16Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia17Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia18Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia19Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia20Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia21Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia22Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia23Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia24Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia25Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia26Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia27Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia6Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia7Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia8Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Aia9Ratjoint inflammation  IDA induced by peptidoglycan-polysaccharideRGD 
Objects Annotated

QTLs
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)

Strains
F344/NCrl  (NA)
LEW/Crl  (Lewis)


Additional Information