ArticleGenome biology2004
Multi-tissue gene-expression analysis in a mouse model of thyroid hormone resistance.
Article in Genome biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 46 citations in OpenAlex.
- A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations.Molecular medicine reports · 2018Article
- Differential transcriptome regulation by 3,5-T2 and 3',3,5-T3 in brain and liver uncovers novel roles for thyroid hormones in tilapia.Scientific reports · 2017Article
- Studies of complex biological systems with applications to molecular medicine: the need to integrate transcriptomic and proteomic approaches.Journal of biomedicine & biotechnology · 2011Review
- Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome.Human molecular genetics · 2010Article
- Nexus between epidermolysis bullosa and transcriptional regulation by thyroid hormone in epidermal keratinocytes.Clinical and translational science · 2008Article
- Novel functions of thyroid hormone receptor mutants: beyond nucleus-initiated transcription.Steroids · 2007Review
- Sarcolipin and phospholamban mRNA and protein expression in cardiac and skeletal muscle of different species.The Biochemical journal · 2005Article
- An unliganded thyroid hormone beta receptor activates the cyclin D1/cyclin-dependent kinase/retinoblastoma/E2F pathway and induces pituitary tumorigenesis.Molecular and cellular biology · 2005Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundResistance to thyroid hormone (RTH) is caused by mutations of the thyroid hormone receptor beta (TRbeta) gene. To understand the transcriptional program underlying TRbeta 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.
resultsWe analyzed transcript levels in cerebellum, heart and white adipose tissue from a knock-in mouse (TRbetaPV/PV mouse) that harbors a human mutation (referred to as PV) and faithfully reproduces human RTH. Because TRbetaPV/PV mice have elevated thyroid hormone (T3), to define T3-responsive genes in the context of normal TRbeta, we also analyzed T3 effects in hyperthyroid wild-type gender-matched littermates. Microarray analysis revealed 163 genes responsive to T3 treatment and 187 genes differentially expressed between TRbetaPV/PV mice and wild-type littermates. Both the magnitude and gene make-up of the transcriptional response varied widely across tissues and conditions. We identified genes modulated in T3-dependent PV-independent, T3- and PV-dependent, and T3-independent PV-dependent pathways that illuminated the biological consequences of PV action in vivo. Most T3-responsive genes that were dysregulated in the heart and white adipose tissue of TRbetaPV/PV mice were repressed in T3-treated wild-type mice and upregulated in TRbetaPV/PV mice, suggesting the inappropriate activation of T3-suppressed genes in RTH.
conclusionsComprehensive multi-tissue gene-expression analysis uncovered complex multiple signaling pathways that mediate the molecular actions of TRbeta mutants in vivo. In particular, the T3-independent mutant-dependent genomic response unveiled the contribution of a novel 'change-of-function' of TRbeta mutants to the pathogenesis of RTH. Thus, the molecular actions of TRbeta mutants are more complex than previously envisioned.
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