1. Hum Mol Genet. 2003 Sep 1;12(17):2087-96. Epub 2003 Jul 8.
High resolution mapping of an arthritis susceptibility locus on rat chromosome 4,
and characterization of regulated phenotypes.
Ribbhammar U(1), Flornes L, Bäckdahl L, Luthman H, Fossum S, Lorentzen JC.
Author information:
(1)Rheumatology Unit, Center for Molecular Medicine, L8:04, Karolinska Hospital,
S-171 76 Stockholm, Sweden.
The rat Natural Killer cell gene Complex (NKC) encodes molecules that can
regulate immunity. It is located within an interval on DA rat chromosome 4 (RNO4)
that is linked to immune-mediated inflammatory joint diseases, including
oil-induced arthritis (OIA). We aimed to test the hypothesis that NKC regulates
arthritis, by performing advanced mapping of arthritis and additional phenotypes
induced by an intradermal injection of incomplete Freund's adjuvant-oil.
Reciprocal transfer of RNO4 intervals established that alleles from DA confer
arthritis susceptibility to inbred LEW.1AV1 and PVG.1AV1 rats, whereas LEW.1AV1
and PVG.1AV1 alleles confer resistance to inbred DA. Subcongenic strains with
PVG.1AV1 alleles introduced on DA allowed mapping of disease predisposition to
0.8 cM on the cytogenetic band 4q42, within the quantitative trait locus
oil-induced arthritis-2 (Oia2), but outside the NKC. Alleles in Oia2 regulated
arthritis in an additive fashion, and determined arthritis incidence, severity
and day of onset, in both males and females. Besides macroscopic
joint-inflammation, Oia2 also regulated other oil-induced phenotypes, including
lymphoplasia and plasma levels of the inflammation marker alpha1-acid
glycoprotein. The high-impact Oia2 region harbors gene sequences similar to human
C3AR1, Ribosomal protein L7, DNAJA2, C-type lectins, C1s and CD163. These
candidate disease genes may be of general interest, given that rat 4q42, and the
syntenic mouse 6F2 and human 12p13 regions are linked to several inflammatory
diseases, including rheumatoid arthritis.
PMID: 12915467 [PubMed - indexed for MEDLINE]
PUBMED: 12915467
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