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| Status |
Public on Jul 24, 2003 |
| Title |
Cardiac hypertrophy related to the phosphoinositide 3-kinase signaling pathway |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The insulin/IGF-IRS-PI3K-Akt pathway is highly conserved in evolution. To test whether this signaling cascade determines organ size in vertebrates, we have recently created mouse lines transgenic for constitutively active (caPI3K) and dominant-negative forms of PI3K (dnPI3K) (Shioi et al., 2000). Transgene expression is driven by the cardiac-specific a -myosin heavy chain (MHC) promoter. Both transgenic lines are characterized by moderate but highly consistent changes in heart size, despite the fact that body weight and the size of other organs are completely normal. caPI3K transgenic animals have hearts 20% larger than those of wild type littermates, whereas dnPI3K mice have hearts that are 17% smaller. The observed changes in heart size correlate with an appropriate increase or decrease in the size of transgenic cardiomyocytes. These hearts do not have cardiomyopathic changes, since the contractile function of transgenic hearts is normal, and signs of necrosis, apoptosis, or interstitial fibrosis are absent (see Physiology). These data suggest an autonomous role for PI3K in cell size regulation. Our goal is now to determine how activation of this system translates into changes in cell size by identifying the trigger and components of this signaling cascade.
Heterozygous caPI3K (constitutively active PI3K) and dnPI3K (dominant-negative PI3K) transgenic female mice (5-14 months) compared with non-transgenic littermates. Transgene expression driven by the a -myosin heavy chain (a -MHC) promoter.
Keywords: other
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| Contributor(s) |
Schinke M, Brown J, Izumo S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jul 24, 2003 |
| Last update date |
Feb 18, 2018 |
| Contact name |
Martina Schinke |
| URL |
http://www.cardiogenomics.org
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| Organization name |
Harvard University
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| Department |
Bauer Center for Genomic Research
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| Lab |
Cardiogenomics
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| Street address |
7 Divinity Ave
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA85535 |
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