tailieunhanh - Multi-tissue gene-expression analysis in a mouse model of thyroid hormone resistance

Genome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, Singapore, 138672. †National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ‡Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892-4264, USA. Correspondence: Sheue-yann Cheng. E-mail: sycheng@ | Research Open Access Multi-tissue gene-expression analysis in a mouse model of thyroid hormone resistance Lance D Miller Peter McPhie Hideyo Suzuki Yasuhito Kato Edison T Liu and Sheue-yann Cheng Addresses Genome Institute of Singapore Agency for Science Technology and Research 60 Biopolis Street Singapore 138672. National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD 20892 USA. laboratory of Molecular Biology National Cancer Institute Bethesda MD 20892-4264 USA. Correspondence Sheue-yann Cheng. E-mail sycheng@ Published 29 April 2004 Genome Biology 2004 5 R3 1 The electronic version of this article is the complete one and can be found online at http 2004 5A5 R31 Received 19 February 2004 Revised 16 March 2004 Accepted 1 April 2004 2004 Miller et al. licensee BioMed Central Ltd. This is an Open Access article verbatim copying and redistribution of this article are permitted in all media for any purpose provided this notice is preserved along with the article s original URL. Abstract Background Resistance to thyroid hormone RTH is caused by mutations of the thyroid hormone receptor p TRP gene. To understand the transcriptional program underlying TRP mutant-induced phenotypic expression of RTH cDNA microarrays were used to profile the expression of 11 500 genes in a mouse model of human RTH. Results We analyzed transcript levels in cerebellum heart and white adipose tissue from a knockin mouse TRpPV PV mouse that harbors a human mutation referred to as PV and faithfully reproduces human RTH. Because TRpPV PV mice have elevated thyroid hormone T3 to define T3-responsive genes in the context of normal TRp we also analyzed T3 effects in hyperthyroid wildtype gender-matched littermates. Microarray analysis revealed 163 genes responsive to T3 treatment and 187 genes differentially expressed between TRpPV PV mice and wild-type littermates. Both the magnitude and gene make-up of the .