RGD Reference Report - COLLAGEN-INDUCED ARTHRITIS SEVERITY LOCI ON RAT CHROMOSOME 10 (RNO10) ALSO REGULATE DISEASE IN THREE OTHER EXPERIMENTALLY INDUCED MODELS OF ARTHRITIS - Rat Genome Database

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COLLAGEN-INDUCED ARTHRITIS SEVERITY LOCI ON RAT CHROMOSOME 10 (RNO10) ALSO REGULATE DISEASE IN THREE OTHER EXPERIMENTALLY INDUCED MODELS OF ARTHRITIS

Authors: Joe, B  Wilder, RL 
Citation: Joe B., etal. 2000 Arthritis Rheum 43:S233
RGD ID: 61519

Adjuvants are components of most, if not all, inducing agents in experimental animal arthritis models. Collagen-induced arthritis (CIA) in rats is an animal model resembling rheumatoid arthritis (RA), in which an emulsion of type II collagen in incomplete Freund's adjuvant (IFA) injected intradermally into susceptible rat strains, such as DA, causes symmetrical erosive Inflammation in the joints. Among the non-MHC quantitative trait loci (QTLs) that regulate CIA in rats, Cia5 on RNO10 is particularly interesting. It regulates arthritis severity in (DA x F344) F2 rats, (DA x BN) F2 rats and also in DA.F344(Cia5) congenic and DA.F344(Cia5a) sub-congenic rats. Severity of CIA is significantly lower in the Cia5 congenic and Cia5a sub-congenic rats than DA controls. To address issues of specificity of the regulatory effects of Cia5 and Cia5a, we compared the phenotypic responses of DA.F344(Cia5) congenic and DA.F344(Cia5a) sub-congenic rats for susceptibility and severity to three additional models in which adjuvants are used: mycobacterial adjuvant-induced arthritis (Mbt-AIA), pristane-induced arthritis (PIA) and IFA-induced arthritis or oil-induced arthritis (OIA). Pristane and IFA are oil-based adjuvants without additives. They are considered weaker adjuvants compared to complete Freund's adjuvant (CFA), which contains mycobacteria in IFA. All three adjuvants induced arthritis in DA rats, but not in F344 rats. Severity of all three induced models of arthritis, Mbt-AIA, PIA and OIA, was significantly lower in the DA.F344(Cia5) congenic rats compared to DA controls. Disease lowering effects were most pronounced in OIA and PIA compared to Mbt-AIA. Severity of PIA and OIA, but not Mbt-AIA, was also significantly lower in DA.F344 (Cia5a) sub-congenic rats compared to DA controls. Disease-ameliorating effects of Cia5 on Mbt-AIA alone, but not PIA or OIA, was gender influenced. Like in CIA, less severe Mbt•AIA was observed in male Cia5 congenic rats than in female congenic rats. Unlike CIA where female DA.F344(Cia5a) developed less severe CIA than males, disease lowering effects of Cia5a on PIA, and OIA were not gender-influenced. These results indicate that the regulatory effects of Cia5 and Cia5a are not limited to CIA alone. Much stronger, gender-independent disease-ameliorating effects of Cia5 and Cia5a are observed in DA.F344 QTL congenic rat strains induced to develop arthritis with weaker adjuvants such as Pristane and IFA, but not with stronger adjuvants such as CFA.



Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

QTLs
Aia5  (Adjuvant induced arthritis QTL 5)
Pia10  (Pristane induced arthritis QTL 10)

Objects referenced in this article
QTL Cia5 Collagen induced arthritis QTL 5 Rattus norvegicus
Strain DA.F344-(D10Arb20-D10Arb22)/Arb null Rattus norvegicus
QTL Eau3 Experimental allergic uveoretinitis QTL 3 Rattus norvegicus
QTL Oia3 Oil induced arthritis QTL 3 Rattus norvegicus

Additional Information