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Gene expression profiling of arthritis using a QTL chip reveals a complex gene regulation of the Cia5 region in mice


One of the major quantitative trait loci (QTLs) associated with arthritis in crosses between B10.RIII and RIIIS/J mice is the Cia5 on chromosome 3. Early in the congenic mapping process it was clear that the locus was complex, consisting of several subloci with small effects. Therefore, we developed two novel strategies to dissect a QTL: the partial advanced intercross (PAI) strategy, with which we recently found the Cia5 region to consist of three loci, Cia5, Cia21 and Cia22, and now we introduce the QTL-chip strategy, where we have combined congenic mapping with a QTL-restricted expression profiling using a novel microarray design. The expression of QTL genes was compared between parental and congenic mice in lymph node, spleen and paw samples in five biological replicates and in dye-swapped experiments at three time points during the induction phase of arthritis. The QTL chip approach revealed 4 genes located in Cia21, differently expressed in lymph nodes, and 14 genes in Cia22, located within two clusters. One cluster contains six genes, differently expressed in spleen, and the second cluster contains eight genes, differently expressed in paws. We conclude the QTL-chip strategy to be valuable in the selection of candidate genes to be prioritized for further investigation.

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We thank Isabell Bohlin and Carlos Palestro for help with the animal care, Ildiko Toth and Cecilia Andersson for technical assistance with the RNA preparations and the real-time RT-PCR, respectively, Valérie Lemée and Andreas Abel (Zeptosens) for help with the SensiChip preparations and Vincent Benoit (Zeptosens) for help with the image analysis of the SensiChips. This work was supported by grants from the Swedish Medical Research Council, the Swedish Foundation for Strategic Research, the Swedish Association against Rheumatism, the Crafoord, Lundberg, the Kock and Österlund Foundations and EU FP5 (QLG1-CT-2001-01407 ‘EUROME’).

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Correspondence to M Johannesson.

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Johannesson, M., Olsson, L., Lindqvist, AK. et al. Gene expression profiling of arthritis using a QTL chip reveals a complex gene regulation of the Cia5 region in mice. Genes Immun 6, 575–583 (2005).

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  • quantitative trait locus
  • complex trait mapping
  • microarray
  • collagen-induced arthritis

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