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| Status |
Public on Feb 08, 2007 |
| Title |
Cardiac-specific deletion of ménage-à-trois-1 (MAT1) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The Cdk7/cyclin H/ménage-à-trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by hypertrophic pathways. Using cardiac-specific Cre, we ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally. However, fatal heart failure ensued at 6-8 weeks. By microarray profiling, quantitative RT-PCR, and Western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC-1α failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1α was functionally defective, and PGC-1β likewise was deficient. PGC-1 was shown to interact with MAT1 and Cdk7, in co-precipitation assays. Thus, we demonstrate an unforeseen essential role for MAT1 in operation of the PGC-1 family of co-activators.
Keywords: conditional knockout in mice
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| Overall design |
MAT1F/F mice (Korsisaari et al., 2002) were bred with mice expressing Cre recombinase under the control of the cardiomyocyte-specific α-myosin heavy chain (αMHC) promoter (Gaussin et al., 2002a) and back-bred to MAT1F/F mice to generate the cardiac-specific knockout (αMHC-Cre+/0; MAT1F/F; CKO; Fig. 1A, B). Control mice were αMHC-Cre+/0; MAT1F/+ littermates, differing by the presence of one wild-type MAT1 allele, and excluding Cre-mediated toxicity as a basis for phenotypic disparity. Cardiac RNA samples were analyze at 2 or 4 weeks of age (N = 3-5 for each condition tested.
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| Contributor(s) |
Sano M, Schneider MD |
| Citation(s) |
17276355 |
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| Submission date |
Jan 05, 2007 |
| Last update date |
Feb 18, 2018 |
| Contact name |
Michael Schneider |
| E-mail(s) |
[email protected]
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| Phone |
713-798-6683
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| Fax |
713-798-7437
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| Organization name |
Baylor College of Medicine
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| Department |
Center for Cardiovascular Development
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| Street address |
One Baylor Plaza, Room 506D
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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| Samples (15)
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| GSM154142 |
Heart, MAT1 control, 4 wk, sample 1 |
| GSM154143 |
Heart, MAT1 control, 4 wk, sample 2 |
| GSM154144 |
Heart, MAT1 control, 4 wk, sample 3 |
| GSM154145 |
Heart, MAT1 CKO, 4 wk, sample 1 |
| GSM154146 |
Heart, MAT1 CKO, 4 wk, sample 2 |
| GSM154147 |
Heart, MAT1 CKO, 4 wk, sample 3 |
| GSM154148 |
Heart, MAT1 CKO, 4 wk, sample 4 |
| GSM154149 |
Heart, MAT1 CKO, 4 wk, sample 5 |
| GSM154150 |
Heart, MAT1 control, 2 wk, sample 1 |
| GSM154151 |
Heart, MAT1 control, 2 wk, sample 2 |
| GSM154152 |
Heart, MAT1 control, 2 wk, sample 3 |
| GSM154153 |
Heart, MAT1 CKO, 2 wk, sample 1 |
| GSM154154 |
Heart, MAT1 CKO, 2 wk, sample 2 |
| GSM154155 |
Heart, MAT1 CKO, 2 wk, sample 3 |
| GSM154156 |
Heart, MAT1 CKO, 2 wk, sample 4 |
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| Relations |
| BioProject |
PRJNA98623 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE6662_RAW.tar |
33.1 Mb |
(http)(custom) |
TAR (of CEL) |
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