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Analysis of candidate genes of spontaneous arthritis in mice deficient for interleukin-1 receptor antagonist.

Abstract
Previously, we identified a major quantitative trait locus (QTL) on mouse chromosome 1 that regulates the susceptibility to arthritis in an F2 population generated from arthritis-prone BALB/c and arthritis-resistant DBA/1 mice deficient for interleukin-1 receptor antagonist. To further select candidate genes for the QTL, we analyzed the expression patterns of arthritis in 38 F2 individuals and compared the expression levels of key candidate genes to the parental strains. Two distinct subpopulations of arthritic mice were identified in the 38 F2 mice. One subgroup of diseased mice was characterized by myeloid cell dominant inflammation, whereas the other was mainly associated with increased anti-apoptotic activities of inflammatory cells. Several differentially expressed important candidate genes in parental strains in the QTL region are relevant to myeloid cell, apoptotic activities, or to both. About one-quarter of those genes have been previously linked to arthritis in literature. The present study reveals two distinct subpopulations of arthritic mice with spontaneous arthritis due to deficiency for interleukin-1 receptor antagonist, suggesting that genes with function relevant to myeloid cell and/or apoptotic activities are most likely the key candidate genes for the QTL.
AuthorsYanhong Cao, Caijuan Li, Jian Yan, Feng Jiao, XiaoYun Liu, Karen A Hasty, John M Stuart, Weikuan Gu, Yan Jiao
JournalGenes & genetic systems (Genes Genet Syst) Vol. 87 Issue 2 Pg. 107-13 ( 2012) ISSN: 1880-5779 [Electronic] Japan
PMID22820384 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
Topics
  • Animals
  • Apoptosis
  • Arthritis, Experimental (genetics)
  • Chromosome Mapping
  • Cluster Analysis
  • Computational Biology
  • Crosses, Genetic
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Interleukin 1 Receptor Antagonist Protein (genetics, metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Mice, Knockout
  • Microarray Analysis
  • Quantitative Trait Loci
  • Selection, Genetic

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