Gene expression profiling of arthritis using a qtl chip reveals a complex gene regulation of the cia5 region in mice

ABSTRACT 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

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ACKNOWLEDGEMENTS 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’). AUTHOR INFORMATION Author notes * M Johannesson and L M Olsson: These authors contributed

equally to this work. AUTHORS AND AFFILIATIONS * Section for Medical Inflammation Research, Lund University, Lund, Sweden M Johannesson, L M Olsson, A-K B Lindqvist, L Wester-Rosenlöf & 

R Holmdahl * University of Rostock, Institute of Immunology, Schillingallee, Rostock, Germany S Möller, D Koczan, H-J Thiesen & S Ibrahim Authors * M Johannesson View author publications

You can also search for this author inPubMed Google Scholar * L M Olsson View author publications You can also search for this author inPubMed Google Scholar * A-K B Lindqvist View author

publications You can also search for this author inPubMed Google Scholar * S Möller View author publications You can also search for this author inPubMed Google Scholar * D Koczan View

author publications You can also search for this author inPubMed Google Scholar * L Wester-Rosenlöf View author publications You can also search for this author inPubMed Google Scholar * H-J

Thiesen View author publications You can also search for this author inPubMed Google Scholar * S Ibrahim View author publications You can also search for this author inPubMed Google Scholar

* R Holmdahl View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to M Johannesson. ADDITIONAL INFORMATION Supplementary

Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene). SUPPLEMENTARY INFORMATION SUPPLEMENTARY TABLE 1 (XLS 30 KB) RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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). https://doi.org/10.1038/sj.gene.6364242 Download citation * Received: 08 March 2005 * Revised: 03 June 2005 *

Accepted: 03 June 2005 * Published: 14 July 2005 * Issue Date: 01 October 2005 * DOI: https://doi.org/10.1038/sj.gene.6364242 SHARE THIS ARTICLE Anyone you share the following link with will

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content-sharing initiative KEYWORDS * quantitative trait locus * complex trait mapping * microarray * collagen-induced arthritis