RGD Reference Report - Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats. - Rat Genome Database

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Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats.

Authors: Gulko, PS  Kawahito, Y  Remmers, EF  Reese, VR  Wang, J  Dracheva, SV  Ge, L  Longman, RE  Shepard, JS  Cannon, GW  Sawitzke, AD  Wilder, RL  Griffiths, MM 
Citation: Gulko PS, etal., Arthritis Rheum 1998 Dec;41(12):2122-31
RGD ID: 61063
Pubmed: (View Article at PubMed) PMID:9870869
DOI: Full-text: DOI:10.1002/1529-0131(199812)41:12<2122::AID-ART7>3.0.CO;2-#

OBJECTIVE: To identify novel non-major histocompatibility complex (non-MHC) genetic loci controlling the severity of homologous rat type II collagen-induced arthritis (CIA). METHODS: We conducted a genome-wide scan to identify CIA regulatory quantitative trait loci (QTL) in an F2 cross between DA (CIA highly susceptible) and ACI (CIA resistant) inbred rats immunized with homologous rat type II collagen (RII). These strains share the MHC/RT1av1 haplotype required for susceptibility to RII-induced CIA. RESULTS: F2 females had higher median arthritis scores than did males. Relative resistance in the males was determined by inheriting either a DA or an ACI Y chromosome and was independent of the source of the X chromosome. In addition, a major QTL was localized on chromosome 2 (Cia7, logarithm of odds score 4.6). Cia7 is in a region that shows linkage conservation with chromosomal regions that regulate autoimmune diabetes and experimental autoimmune encephalomyelitis in mice and multiple sclerosis in humans. CONCLUSION: Sex chromosomes and Cia7 play an important role in regulating CIA in response to RII. This rat model should facilitate positional cloning and functional characterization of regulatory genes that may play a role in several forms of autoimmune disease, including rheumatoid arthritis.

Annotation

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
joint inflammation  (IAGP,QTM)
joint swelling  (IAGP,QTM)
Objects Annotated

QTLs
Cia10  (Collagen induced arthritis QTL 10)
Cia27  (Collagen induced arthritis QTL 27)
Cia7  (Collagen induced arthritis QTL 7)
Cia9  (Collagen induced arthritis QTL 9)

Objects referenced in this article
Marker D2Mit24 D2Mit24 Rattus norvegicus
Marker D2Mit17 D2Mit17 Rattus norvegicus
Marker D2Mit23 D2Mit23 Rattus norvegicus
Marker D2Mgh12 D2Mgh12 Rattus norvegicus
Strain ACI/N A X C 9935, Irish Rattus norvegicus
Strain BBDR/Rhw null Rattus norvegicus
Strain BN BN Rattus norvegicus
Gene Cd2 Cd2 molecule Rattus norvegicus
Gene Cd53 Cd53 molecule Rattus norvegicus
Strain DA/Bkl null Rattus norvegicus
Gene Il12b interleukin 12B Rattus norvegicus
Gene Il6r interleukin 6 receptor Rattus norvegicus
Gene Ngf nerve growth factor Rattus norvegicus
Gene Nras NRAS proto-oncogene, GTPase Rattus norvegicus
Gene Vcam1 vascular cell adhesion molecule 1 Rattus norvegicus

Additional Information