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Series GSE3067 Query DataSets for GSE3067
Status Public on Sep 26, 2005
Title Resistance to thyroid hormone (RTH) and PPARa activation
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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
Contributor(s) Buroker NE, Young ME, Serikawa K, Ge M, Ning X, Wei C, Portman M
Citation(s) 16985257
Submission date Aug 05, 2005
Last update date Feb 11, 2019
Contact name Norman Buroker
Organization name Seattle Children's Hospital
Lab Portman
Street address 4800 Sand Point Way N.E.
City Seattle
State/province WA
ZIP/Postal code 98105
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (28)
GSM67362 Control replicate 1
GSM67363 Control replicate 2
GSM67364 Control replicate 3
BioProject PRJNA93161

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