1. Hum Mol Genet. 2000 Sep 22;9(15):2241-50.
Genetic dissection of a rat model for rheumatoid arthritis: significant gender
influences on autosomal modifier loci.
Furuya T(1), Salstrom JL, McCall-Vining S, Cannon GW, Joe B, Remmers EF,
Griffiths MM, Wilder RL.
Author information:
(1)Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes
of Health, 9000 Rockville Pike, Bethesda, MD 20892-1820, USA.
Rheumatoid arthritis (RA) is a common, chronic, autoimmune, inflammatory disease
that is influenced by genetic factors including gender. Many studies suggest that
the genetic risk for RA is determined by the MHC, in particular class II alleles
with a 'shared epitope' (SE), and multiple non-MHC loci. Other studies indicate
that RA and other autoimmune diseases, in particular insulin-dependent diabetes
mellitus (IDDM) and autoimmune thyroid disease (ATD), share genetic risk factors.
Rat collagen-induced arthritis (CIA) is an experimental model with many features
that resemble RA. The spontaneous diabetes-resistant bio-breeding rat, BB(DR), is
of interest because it is susceptible to experimentally induced CIA, IDDM and
ATD, and it has an SE in its MHC class II allele. To explore the genetics of CIA,
including potential gender influences and the genetic relationships between CIA
and other autoimmune diseases, we conducted a genome-wide scan for CIA regulatory
loci in the F(2) progeny of BB(DR) and CIA-resistant BN rats. We identified 10
quantitative trait loci (QTLs), including 5 new ones (Cia15, Cia16*, Cia17,
Cia18* and Cia19 on chromosomes 9, 10, 18 and two on the X chromosome,
respectively), that regulated CIA severity. We also identified four QTLs,
including two new ones (Ciaa4* and Ciaa5* on chromosomes 4 and 5, respectively),
that regulated autoantibody titer to rat type II collagen. Many of these loci
appeared to be gender influenced, and most co-localized with several other
autoimmune trait loci. Our data support the view that multiple autoimmune
diseases may share genetic risk factors, and suggest that many of these loci are
gender influenced.
PMID: 11001927 [PubMed - indexed for MEDLINE]
PUBMED: 11001927
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