Advanced

Both common and unique susceptibility genes in different rat strains with pristane-induced arthritis.

Lu, Shemin LU ; Nordquist, Niklas; Holmberg, Jens LU ; Olofsson, Peter LU ; Pettersson, Ulf and Holmdahl, Rikard LU (2002) In European Journal of Human Genetics 10(8). p.475-483
Abstract
Pristane-induced arthritis (PIA) in rats is an animal model for rheumatoid arthritis (RA). We have previously identified seven quantitative trait loci (QTLs), which regulate arthritis development using a cross between the susceptible DA strain and the resistant E3 strain of rats (Pia2-8). In the present study the inbred rat strain LEW.1F was used as the susceptible strain in a cross with the E3 strain. The results confirmed the locus Pia4 on chromosome 12, which previously was shown to be associated with PIA, and also with experimental allergic encephalomyelitis, in crosses between the rat strains E3 and DA. On chromosome 1, linked to the albino locus, we identified a novel QTL, Pia9 in the LEW.F1 cross. This locus was associated with... (More)
Pristane-induced arthritis (PIA) in rats is an animal model for rheumatoid arthritis (RA). We have previously identified seven quantitative trait loci (QTLs), which regulate arthritis development using a cross between the susceptible DA strain and the resistant E3 strain of rats (Pia2-8). In the present study the inbred rat strain LEW.1F was used as the susceptible strain in a cross with the E3 strain. The results confirmed the locus Pia4 on chromosome 12, which previously was shown to be associated with PIA, and also with experimental allergic encephalomyelitis, in crosses between the rat strains E3 and DA. On chromosome 1, linked to the albino locus, we identified a novel QTL, Pia9 in the LEW.F1 cross. This locus was associated with arthritis severity in the early phase of disease. A locus on chromosome 16, denoted Pia11, was also associated with arthritis severity in the early phase of the disease. A suggestive locus was detected on chromosome 14, which was associated with arthritis severity at the time when PIA progresses into a chronic phase. Using a congenic LEW.1F strain, which carries E3 alleles at the Pia9 locus, we confirmed that the E3 allele significantly suppresses arthritis severity during the early phase of the disease. The results revealed synergistic effects between different susceptibility loci using ANOVA analysis. These interactions were influenced by gender. Rats with Pia9 alleles from LEW.1F and Pia11 alleles from E3, were shown to suffer from much more severe arthritis in the early stage of the disease. On the other hand, the Pia9 and the suggestive locus on chromosome 14 affected only males during the chronic phase of the disease. These findings provide clues to how genetic factors by themselves, and in interaction with each other, regulate the development of a disease, which displays many similarities to RA. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Human Genetics
volume
10
issue
8
pages
475 - 483
publisher
Nature Publishing Group
external identifiers
  • wos:000177267300005
  • pmid:12111642
  • scopus:0035991635
ISSN
1476-5438
DOI
10.1038/sj.ejhg.5200832
language
English
LU publication?
yes
id
834c6dbd-7a8d-4fae-845b-4e82e72c1dcf (old id 109228)
date added to LUP
2007-07-17 10:44:13
date last changed
2017-07-23 03:57:57
@article{834c6dbd-7a8d-4fae-845b-4e82e72c1dcf,
  abstract     = {Pristane-induced arthritis (PIA) in rats is an animal model for rheumatoid arthritis (RA). We have previously identified seven quantitative trait loci (QTLs), which regulate arthritis development using a cross between the susceptible DA strain and the resistant E3 strain of rats (Pia2-8). In the present study the inbred rat strain LEW.1F was used as the susceptible strain in a cross with the E3 strain. The results confirmed the locus Pia4 on chromosome 12, which previously was shown to be associated with PIA, and also with experimental allergic encephalomyelitis, in crosses between the rat strains E3 and DA. On chromosome 1, linked to the albino locus, we identified a novel QTL, Pia9 in the LEW.F1 cross. This locus was associated with arthritis severity in the early phase of disease. A locus on chromosome 16, denoted Pia11, was also associated with arthritis severity in the early phase of the disease. A suggestive locus was detected on chromosome 14, which was associated with arthritis severity at the time when PIA progresses into a chronic phase. Using a congenic LEW.1F strain, which carries E3 alleles at the Pia9 locus, we confirmed that the E3 allele significantly suppresses arthritis severity during the early phase of the disease. The results revealed synergistic effects between different susceptibility loci using ANOVA analysis. These interactions were influenced by gender. Rats with Pia9 alleles from LEW.1F and Pia11 alleles from E3, were shown to suffer from much more severe arthritis in the early stage of the disease. On the other hand, the Pia9 and the suggestive locus on chromosome 14 affected only males during the chronic phase of the disease. These findings provide clues to how genetic factors by themselves, and in interaction with each other, regulate the development of a disease, which displays many similarities to RA.},
  author       = {Lu, Shemin and Nordquist, Niklas and Holmberg, Jens and Olofsson, Peter and Pettersson, Ulf and Holmdahl, Rikard},
  issn         = {1476-5438},
  language     = {eng},
  number       = {8},
  pages        = {475--483},
  publisher    = {Nature Publishing Group},
  series       = {European Journal of Human Genetics},
  title        = {Both common and unique susceptibility genes in different rat strains with pristane-induced arthritis.},
  url          = {http://dx.doi.org/10.1038/sj.ejhg.5200832},
  volume       = {10},
  year         = {2002},
}