title: In vivo expression of a conditional TGF-beta1 transgene: no evidence for TGF-beta1 transgene expression in SM22alpha-tTA transgenic mice.
abstract: 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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA, USA.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Ramtin
authors.initials: R
authors.lastname: Agah
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Frutkin
authors.forename: Michal
authors.initials: M
authors.lastname: Kremen
authors.forename: Haikun
authors.initials: H
authors.lastname: Shi
authors.forename: David A
authors.initials: DA
authors.lastname: Dichek
mesh_terms: D000483:Alleles; D000818:Animals; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; C058992:Tagln protein, mouse; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001616:beta-Galactosidase; D004318:Doxycycline