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Accession: PRJNA93161 ID: 93161

Mus musculus (house mouse)

Resistance to thyroid hormone (RTH) and PPARa activation

See Genome Information for Mus musculus
In this study we used the d337T TRb transgenic mouse that has been created to reproduce the human genetic disease known as resistance to thyroid hormone (RTH) as a model to determine if the d337T TRb mutation would have an effect on PPARa activation. A single amino acid deletion (d337T) abrogates thyroid hormone (T3) binding and transforms the thyroid hormone receptor (TRb) into a constitutive repressor. The principle goal was to determine if T3 regulates myocardial energy metabolism through its nuclear receptors. We introduced a known PPARa activator (WY14, 643) into control and d337T TRb transgenic mice then examined cardiac gene expression using Affymetrix 430_2 expression arrays and RT-PCR. We compared the gene expression of PPARa, RXRb and TRa,b and three PPARa target genes among four studies groups [control, control with WY14, 643, d337T TRb, and d337T TRb with WY14, 643] consisting of seven mice per group. Microarray analysis revealed that these genes responded to the WY14, 643 treatments of control and d337T TRb mice. Analysis of the array and RT-PCR data indicates that mRNA expression levels of PPARa and mRXRb decrease after a six hour drug treatment in both control and d337T TRb mice (P<0.01) as did the array mRNA expression levels for TRa & b (P<0.025). Three target genes (AMPD3, PDK4 and UCP3) of PPARa were up regulated in control and down regulated in the d337T TRb transgenic mouse, indicating a direct action on these metabolic genes when the TRb becomes a repressor. In conclusion, PPARa activation by WY14, 643 has a positive effect on control mice and a negative effect on the TRb transgenic mice which supports our hypothesis that T3 regulates myocardial energy metabolism through its nuclear receptors. Keywords: treatment and deletion effects Overall design: 7 control, 7 deletion strain individuals, 7 controls with a PPARalpha activator, 7 deletion strain individuals with a PPARalpha activator
AccessionPRJNA93161; GEO: GSE3067
Data TypeTranscriptome or Gene expression
ScopeMultiisolate
OrganismMus musculus[Taxonomy ID: 10090]
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus; Mus musculus
PublicationsBuroker NE et al., "The dominant negative thyroid hormone receptor beta-mutant {Delta}337T alters PPAR{alpha} signaling in heart.", Am J Physiol Endocrinol Metab, 2007 Feb;292(2):E453-60
SubmissionRegistration date: 26-Sep-2005
Portman, Seattle Children's Hospital
RelevanceModel Organism
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PubMed1
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GEO DataSets2
GEO Data Details
ParameterValue
Data volume, Spots1262828
Data volume, Processed Mbytes33

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    Resistance to thyroid hormone (RTH) and PPARa activation
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