1. Arthritis Rheum. 2002 Apr;46(4):1075-85.
Evaluation of quantitative trait loci regulating severity of mycobacterial
adjuvant-induced arthritis in monocongenic and polycongenic rats: identification
of a new regulatory locus on rat chromosome 10 and evidence of overlap with
rheumatoid arthritis susceptibility loci.
Joe B(1), Cannon GW, Griffiths MM, Dobbins DE, Gulko PS, Wilder RL, Remmers EF.
Author information:
(1)National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH,
Bethesda, Maryland 20892, USA.
OBJECTIVE: To evaluate the regulatory potential of genetic loci controlling
Mycobacterium butyricum adjuvant-induced arthritis (Mbt-AIA) using mono- and
polycongenic rats.
METHODS: Of 4 quantitative trait loci (QTLs) that regulate Mbt-AIA, F344 alleles
at 3 of these loci, Aia1, Aia2, and Aia3, are associated with lower arthritis
severity, whereas F344 alleles at Aia4 are associated with greater arthritis
severity. In this study, we constructed congenic lines by transferring 1 or more
of the F344 genomic segments containing Aia1, Aia2, and Aia3 onto the DA genome.
We comparatively evaluated their responses to Mbt-AIA with the responses of
parental DA and F344 rats.
RESULTS: Aia1, encompassing the rat major histocompatibility complex, reduced
arthritis severity in monocongenic rats of both sexes. The arthritis-lowering
effects of Aia2 and Aia3 were sex-influenced and were therefore observed in only
males and only females, respectively. Polycongenic rats containing F344 genomic
regions at Aia1, Aia2, and Aia3 developed Mbt-AIA of relatively greater severity
than did F344 rats, implying that in DA and F344 rats, there could be other
Mbt-AIA loci in addition to Aia1, Aia2, Aia3, and Aia4. To test the possibility
that some of these Mbt-AIA-regulatory loci may colocalize with other arthritis
QTLs, we evaluated Mbt-AIA in DA.F344 monocongenic rats containing
collagen-induced arthritis QTLs. Cia5 (the QTL region on chromosome 10), but not
Cia5a, Cia4, or Cia6, also regulated Mbt-AIA, and was named Aia5.
CONCLUSION: F344 genomic regions at Aia1, Aia2, and Aia3 and the newly identified
Aia5 contain genes that reduce Mbt-AIA severity in DA rats. These
Mbt-AIA-regulatory loci overlap rheumatoid arthritis-susceptibility loci in
humans.
PMID: 11953987 [PubMed - indexed for MEDLINE]
PUBMED: 11953987
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