Document Detail


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.
MedLine Citation:
PMID:  11003387     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
B Joe; E F Remmers; D E Dobbins; J L Salstrom; T Furuya; S Dracheva; P S Gulko; G W Cannon; M M Griffiths; R L Wilder
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Immunogenetics     Volume:  51     ISSN:  0093-7711     ISO Abbreviation:  Immunogenetics     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-20     Completed Date:  2000-10-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0420404     Medline TA:  Immunogenetics     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  930-44     Citation Subset:  IM    
Affiliation:
Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Congenic
Arthritis, Rheumatoid / chemically induced,  genetics*,  physiopathology
Chromosome Mapping
Collagen / immunology
Cricetinae
Female
Humans
Linkage (Genetics)
Male
Mice
Quantitative Trait, Heritable*
Rats
Rats, Inbred F344
Regulatory Sequences, Nucleic Acid
Sex Factors
Time Factors
Chemical
Reg. No./Substance:
9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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