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.

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General

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

Experimental Arthritis (IDA)

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

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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.