In vivo expression of a conditional TGF-β1 transgene: no evidence for TGF-β1 transgene expression in SM22α-tTA transgenic mice
| Autor: | Ramtin Agah, Andrew D. Frutkin, Ming Xiao, David A. Dichek, Michal Kremen, Sunyoung Lee, Haikun Shi |
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| Rok vydání: | 2006 |
| Předmět: |
Transcriptional Activation
Genetically modified mouse Vascular smooth muscle Transgene Muscle Proteins Mice Transgenic Biology Article Muscle Smooth Vascular Transforming Growth Factor beta1 Mice Transactivation Transforming Growth Factor beta In vivo medicine Animals Molecular Biology Alleles Doxycycline Microfilament Proteins Heart beta-Galactosidase Molecular biology Cell biology medicine.anatomical_structure Gene Expression Regulation Cardiology and Cardiovascular Medicine Transforming growth factor medicine.drug Artery |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 40:148-156 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/j.yjmcc.2005.09.015 |
| Popis: | Transforming growth beta-1 (TGF-beta1) appears to play a critical role in the regulation of arterial intimal growth and the development of atherosclerosis. TGF-beta1 is expressed at increased levels in diseased arteries; however, its role in disease development remains controversial. Experiments in which TGF-beta1 is overexpressed in the artery wall of transgenic mice could clarify the role of TGF-beta1 in the development or prevention of vascular disease. However, constitutive overexpression of a TGF-beta1 transgene in the mouse artery wall is embryonically lethal. Therefore, to overexpress TGF-beta1 in the artery wall of adult mice, we generated mice that were transgenic for a conditional, tetracycline operator (tetO)-driven TGF-beta1 allele. These mice were viable, and when crossed with mice expressing a tetracycline-regulated transactivator (tTA) in the heart, expressed the TGF-beta1 transgene in a cardiac-restricted and doxycycline-dependent manner. Nevertheless, breeding of the tetO-TGF-beta1 transgene into three lines of mice transgenic for a smooth muscle-targeted tTA (SM22alpha-tTA mice; reported elsewhere to transactivate tetO-driven alleles in smooth muscle cells of large arteries) did not yield expression of the TGF-beta1 transgene. Moreover, tTA expression was not detected in aortae of the SM22alpha-tTA mice. Transgenic mice that express tTA at high levels in vascular smooth muscle and reliably transactivate tetO-driven transgenes would be useful for deciphering the role of TGF-beta1 (or other proteins) in normal arterial physiology and in the development of arterial disease. Currently available SM22alpha-tTA mice were not useful for this purpose. Generation of higher-expressing lines of SM22alpha-tTA mice appears warranted. |
| Databáze: | OpenAIRE |
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