In vivo expression of a conditional TGF-β1 transgene: no evidence for TGF-β1 transgene expression in SM22α-tTA transgenic mice

Transforming growth beta-1 (TGF-β1) appears to play a critical role in the regulation of arterial intimal growth and the development of atherosclerosis. TGF-β1 is expressed at increased levels in diseased arteries; however, its role in disease development remains controversial. Experiments in which TGF-β1 is overexpressed in the artery wall of transgenic mice could clarify the role of TGF-β1 in the development or prevention of vascular disease. However, constitutive overexpression of a TGF-β1 transgene in the mouse artery wall is embryonically lethal. Therefore, to overexpress TGF-β1 in the artery wall of adult mice, we generated mice that were transgenic for a conditional, tetracycline operator (tetO)-driven TGF-β1 allele. These mice were viable, and when crossed with mice expressing a tetracycline-regulated transactivator (tTA) in the heart, expressed the TGF-β1 transgene in a cardiac-restricted and doxycycline-dependent manner. Nevertheless, breeding of the tetO-TGF-β1 transgene into three lines of mice transgenic for a smooth muscle-targeted tTA (SM22α-tTA mice; reported elsewhere to transactivate tetO-driven alleles in smooth muscle cells of large arteries) did not yield expression of the TGF-β1 transgene. Moreover, tTA expression was not detected in aortae of the SM22α-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-β1 (or other proteins) in normal arterial physiology and in the development of arterial disease. Currently available SM22α-tTA mice were not useful for this purpose. Generation of higher-expressing lines of SM22α-tTA mice appears warranted.