RGD Reference Report - Genetic dissection of collagen-induced arthritis in Chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences. - Rat Genome Database

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Genetic dissection of collagen-induced arthritis in Chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences.

Authors: Joe, B  Remmers, EF  Dobbins, DE  Salstrom, JL  Furuya, T  Dracheva, S  Gulko, PS  Cannon, GW  Griffiths, MM  Wilder, RL 
Citation: Joe B, etal., Immunogenetics 2000 Sep;51(11):930-44.
RGD ID: 631168
Pubmed: PMID:11003387   (View Abstract at PubMed)

Rat Chromosome 10 (RNO10) harbors Cia5, a non-MHC quantitative trait locus (QTL) that regulates the severity of type II collagen-induced arthritis (CIA) in DAxF344 and DAxBN F2 rats. CIA is an animal model with many features that resemble rheumatoid arthritis. To facilitate analysis of Cia5 independently of the other CIA regulatory loci on other chromosomes, DA recombinant QTL speed congenic rats, DA.F344(Cia5), were generated. These QTL congenic rats have a large chromosomal segment containing Cia5 (interval size < or =80.1 cM) from CIA-resistant F344 rats introgressed into their genome. Phenotypic analyses of these rats for susceptibility and severity of CIA confirmed that Cia5 is an important disease-modifying locus. CIA severity was significantly lower in the Cia5 congenic rats than in DA controls. We also generated DA Cia5 speed sub-congenic rats, DA.F344(Cia5a), which had a smaller segment of the F344 genome, Cia5a, comprising only the distal q-telomeric end (interval size < or = 22.5 cM) of Cia5, introgressed into their genome. DA.F344(Cia5a) sub-congenic rats also exhibited reduced CIA disease severity compared with the parental DA rats. The regulatory effects in both congenic strains were sex influenced. The disease-ameliorating effect of the larger fragment, Cia5, was greater in males than in females, but the effect of the smaller fragment, Cia5a, was greater in females. We also present an improved genetic linkage map covering the Cia5/Cia5a region, which we have integrated with two rat radiation hybrid maps. Comparative homology analysis of this genomic region with mouse and human chromosomes was also undertaken. Regulatory loci for multiple autoimmune/inflammatory diseases in rats (RNO10), mice (MMU11), and humans (HSA17 and HSA5q23-q31) map to chromosomal segments homologous to Cia5 and Cia5a.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Arthritis  IDA 631168; 631168; 631168; 631168 RGD 
Experimental Arthritis inducedIAGPtype II collagen631168; 631168; 631168 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
arthritis inducedIAGPtype II collagen631168; 631168; 631168 RGD 
joint swelling  QTM 631168; 631168; 631168; 631168 RGD 

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Objects Annotated

QTLs
Cia20  (Collagen induced arthritis QTL 20)
Cia21  (Collagen induced arthritis QTL 21)
Cia22  (Collagen induced arthritis QTL 22)
Cia23  (Collagen induced arthritis QTL 23)

Objects referenced in this article
QTL Cia5 Collagen induced arthritis QTL 5 Rattus norvegicus
Strain DA/Bkl null Rattus norvegicus

Additional Information