1. Immunogenetics. 2000 Sep;51(11):930-44.
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.
Joe B(1), Remmers EF, Dobbins DE, Salstrom JL, Furuya T, Dracheva S, Gulko PS,
Cannon GW, Griffiths MM, Wilder RL.
Author information:
(1)Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD
20892, USA.
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.
PMID: 11003387 [PubMed - indexed for MEDLINE]
PUBMED: 11003387
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