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High resolution mapping of an arthritis susceptibility locus on rat chromosome 4, and characterization of regulated phenotypes

Ribbhammar, U; Flornes, L; Backdahl, L; Luthman, Holger LU ; Fossum, S and Lorentzen, JC (2003) In Human Molecular Genetics 12(17). p.2087-2096
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
12
issue
17
pages
2087 - 2096
publisher
Oxford University Press
external identifiers
  • wos:000185321300001
  • pmid:12915467
  • scopus:0041377854
ISSN
0964-6906
DOI
10.1093/hmg/ddg224
language
English
LU publication?
yes
id
6dcaf262-68eb-4b32-bbc5-01a306b822e3 (old id 301299)
date added to LUP
2007-09-20 15:35:09
date last changed
2018-10-03 10:07:06
@article{6dcaf262-68eb-4b32-bbc5-01a306b822e3,
  abstract     = {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.},
  author       = {Ribbhammar, U and Flornes, L and Backdahl, L and Luthman, Holger and Fossum, S and Lorentzen, JC},
  issn         = {0964-6906},
  language     = {eng},
  number       = {17},
  pages        = {2087--2096},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {High resolution mapping of an arthritis susceptibility locus on rat chromosome 4, and characterization of regulated phenotypes},
  url          = {http://dx.doi.org/10.1093/hmg/ddg224},
  volume       = {12},
  year         = {2003},
}