RGD Reference Report - Common genetic determinants of uveitis shared with other autoimmune disorders. - Rat Genome Database

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Common genetic determinants of uveitis shared with other autoimmune disorders.

Authors: Mattapallil, MJ  Sahin, A  Silver, PB  Sun, SH  Chan, CC  Remmers, EF  Hejtmancik, JF  Caspi, RR 
Citation: Mattapallil MJ, etal., J Immunol. 2008 May 15;180(10):6751-9.
RGD ID: 2296064
Pubmed: PMID:18453595   (View Abstract at PubMed)
PMCID: PMC2493541   (View Article at PubMed Central)

Uveitis is a complex multifactorial autoimmune disease of the eye characterized by inflammation of the uvea and retina, degeneration of the retina, and blindness in genetically predisposed patients. Using the rat model of experimental autoimmune uveitis (EAU), we previously identified three quantitative trait loci (QTL) associated with EAU on rat chromosomes 4, 12, and 10 (Eau1, Eau2, and Eau3). The primary goal of the current study is to delineate additional non-MHC chromosomal regions that control susceptibility to EAU, and to identify any QTLs that overlap with the QTLs of other autoimmune diseases. Using a set of informative microsatellite markers and F(2) generations of resistant and susceptible MHC class II-matched rat strains (F344 and LEW), we have identified several new significant or suggestive QTLs on rat chromosomes 2, 3, 7, 10, and 19 that control susceptibility to EAU. A protective allele was identified in the susceptible LEW strain in the Eau5 locus at D7Wox18, and epistatic interactions between QTLs were found to influence the severity of disease. The newly identified regions (Eau4 through Eau9) colocalize with the genetic determinants of other autoimmune disease models, and to disease-regulating syntenic regions identified in autoimmune patients on human chromosomes 4q21-31, 5q31-33, 16q22-24, 17p11-q12, 20q11-13, and 22q12-13. Our results suggest that uveitis shares some of the pathogenic mechanisms associated with other autoimmune diseases, and lends support to the "common gene, common pathway" hypothesis for autoimmune disorders.



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Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Eau4Ratabnormal uvea morphology  IDA induced by peptide R16RGD 
Eau5Ratabnormal uvea morphology  IDA induced by peptide R16RGD 
Eau6Ratabnormal uvea morphology  IDA induced by peptide R16RGD 
Eau7Ratabnormal uvea morphology  IDA induced by peptide R16RGD 
Eau8Ratabnormal uvea morphology  IDA induced by peptide R16RGD 
Eau9Ratabnormal uvea morphology  IDA induced by peptide R16RGD 
Eau5Ratdecreased susceptibility to experimental autoimmune uveoretinitis  IDA decreased susceptibility due to F alleleRGD 
Eau6Ratdecreased susceptibility to experimental autoimmune uveoretinitis  IDA decreased susceptibility due to LEW alleleRGD 
Eau7Ratdecreased susceptibility to experimental autoimmune uveoretinitis  IDA decreased susceptibility due to F alleleRGD 
Eau8Ratdecreased susceptibility to experimental autoimmune uveoretinitis  IDA  RGD 
Eau9Ratdecreased susceptibility to experimental autoimmune uveoretinitis  IDA decreased susceptibility due to F alleleRGD 
Eau1Rateye inflammation  IDA  RGD 
Eau2Rateye inflammation  IDA  RGD 
Eau3Rateye inflammation  IDA  RGD 
Eau4Rateye inflammation  IDA  RGD 
Eau5Rateye inflammation  IDA  RGD 
Eau6Rateye inflammation  IDA  RGD 
Eau7Rateye inflammation  IDA  RGD 
Eau8Rateye inflammation  IDA  RGD 
Eau9Rateye inflammation  IDA  RGD 
Eau4Ratincreased susceptibility to experimental autoimmune uveoretinitis  IDA induced by peptide R16RGD 
Eau5Ratincreased susceptibility to experimental autoimmune uveoretinitis susceptibilityIDA due to L alleleRGD 
Eau7Ratincreased susceptibility to experimental autoimmune uveoretinitis susceptibilityIDA due to L alleleRGD 
Eau9Ratincreased susceptibility to experimental autoimmune uveoretinitis susceptibilityIDA due to L alleleRGD 
LEW/SsNHsdRatincreased susceptibility to experimental autoimmune uveoretinitis inducedIAGPR16 peptide of interphotoreceptor retinoid-binding proteincompared to F344/NHsdRGD 
Objects Annotated

QTLs
Eau1  (Experimental allergic uveoretinitis QTL 1)
Eau2  (Experimental allergic uveoretinitis QTL 2)
Eau3  (Experimental allergic uveoretinitis QTL 3)
Eau4  (Experimental allergic uveoretinitis QTL 4)
Eau5  (Experimental allergic uveoretinitis QTL 5)
Eau6  (Experimental allergic uveoretinitis QTL 6)
Eau7  (Experimental allergic uveoretinitis QTL 7)
Eau8  (Experimental allergic uveoretinitis QTL 8)
Eau9  (Experimental allergic uveoretinitis QTL 9)

Strains
F344/NHsd  (F344/NHsd)
LEW/NHsd  (NA)
LEW/SsNHsd  (NA)

Objects referenced in this article
QTL Cia10 Collagen induced arthritis QTL 10 Rattus norvegicus
QTL Cia14 Collagen induced arthritis QTL 14 Rattus norvegicus
QTL Eae18 Experimental allergic encephalomyelitis QTL 18 Rattus norvegicus
QTL Eae3 Experimental allergic encephalomyelitis QTL 3 Rattus norvegicus
QTL Iddm13 Insulin dependent diabetes mellitus QTL 13 Rattus norvegicus
QTL Niddm14 Non-insulin dependent diabetes mellitus QTL 14 Rattus norvegicus
QTL Pia15 Pristane induced arthritis QTL 15 Rattus norvegicus

Additional Information