RGD Reference Report - Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats. - Rat Genome Database

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Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats.

Authors: Sun, SH  Silver, PB  Caspi, RR  Du, Y  Chan, CC  Wilder, RL  Remmers, EF 
Citation: Sun SH, etal., Int Immunol 1999 Apr;11(4):529-34
RGD ID: 61073
Pubmed: PMID:10323205   (View Abstract at PubMed)

The present study attempts to identify specific genetic loci contributing to experimental autoimmune uveoretinitis (EAU) susceptibility in F2 progeny of resistant Fischer (F344/N) and susceptible Lewis (LEW/N) inbred rats. F2 progeny of F344/N x LEW/N inbred rats were immunized with the R16 peptide of interphotoreceptor retinoid-binding protein (IRBP). A genome-wide scan was conducted using 125 simple sequence length polymorphism markers in selected F2 animals that developed severe eye disease or remained unaffected to identify phenotype:genotype co-segregation. The F2 population (n = 1287) demonstrated a wide range of histologically assessed EAU scores (assessed on a scale of 0-4). The disease incidence and severity were not consistent with a simple Mendelian inheritance model. Of the F2 hybrid rats, 60% developed EAU, implying the existence of a potent susceptibility locus with incomplete penetrance associated with the LEW genome or a more complex polygenic model of inheritance. Two genomic regions, on chromosomes 4 and 12, showed strong genetic linkage to the EAU phenotype (P < 0.0016), suggesting the presence of susceptibility loci in these chromosomal regions. In conclusion, we have identified two genomic candidate intervals from D4Arb8 to D4Mit17 on chromosome 4 and from the chromosome end to D12Arb8 on chromosome 12, that appear to influence EAU susceptibility in LEW/F344 rats. Further analysis of these genomic regions may lead to identification of the susceptibility genes and to characterization of their function.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Eau1RatExperimental Autoimmune Uveitis  IDA  RGD 
Eau2RatExperimental Autoimmune Uveitis  IDA  RGD 
Eau3RatExperimental Autoimmune Uveitis  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Eau1Ratabnormal uvea morphology  QTM  RGD 
Eau2Ratabnormal uvea morphology  QTM  RGD 
Eau3Ratabnormal uvea morphology  QTM  RGD 
Objects Annotated

Eau1  (Experimental allergic uveoretinitis QTL 1)
Eau2  (Experimental allergic uveoretinitis QTL 2)
Eau3  (Experimental allergic uveoretinitis QTL 3)

F344/NRrrc  (NA)
LEW  (Lewis)

Objects referenced in this article
Marker D4Arb7 D4Arb7 Rattus norvegicus
Marker D4Arb8 D4Arb8 Rattus norvegicus
Marker D10Mit11 D10Mit11 Rattus norvegicus
Marker D4Mit17 D4Mit17 Rattus norvegicus
Marker D10Mit3 D10Mit3 Rattus norvegicus
Marker D12Arb2 D12Arb2 Rattus norvegicus
Marker D12Arb5 D12Arb5 Rattus norvegicus
Marker D10Arb3 D10Arb3 Rattus norvegicus
QTL Aia3 Adjuvant induced arthritis QTL 3 Rattus norvegicus
QTL Aia5 Adjuvant induced arthritis QTL 5 Rattus norvegicus
QTL Cari1 Carrageenan-induced inflammation QTL 1 Rattus norvegicus
QTL Cia12 Collagen induced arthritis QTL 12 Rattus norvegicus
QTL Cia3 Collagen induced arthritis QTL 3 Rattus norvegicus
QTL Cia5 Collagen induced arthritis QTL 5 Rattus norvegicus
Gene Crhr1 corticotropin releasing hormone receptor 1 Rattus norvegicus
Gene Hsd17b1 hydroxysteroid (17-beta) dehydrogenase 1 Rattus norvegicus
QTL Iddm2 Insulin dependent diabetes mellitus QTL 2 Rattus norvegicus
Gene Npy neuropeptide Y Rattus norvegicus
QTL Oia3 Oil induced arthritis QTL 3 Rattus norvegicus
QTL Pia10 Pristane induced arthritis QTL 10 Rattus norvegicus
QTL Pia4 Pristane induced arthritis QTL 4 Rattus norvegicus
Gene Prkca protein kinase C, alpha Rattus norvegicus
QTL Scwia1 Streptococcal cell wall induced arthritis QTL 1 Rattus norvegicus
Gene Stat3 signal transducer and activator of transcription 3 Rattus norvegicus
Gene Tcrb T-cell receptor beta chain Rattus norvegicus
Gene Thy1 Thy-1 cell surface antigen Rattus norvegicus
Gene Tnfaip1 TNF alpha induced protein 1 Rattus norvegicus
Gene Trim25 tripartite motif-containing 25 Rattus norvegicus

Additional Information