title: A new dual-promoter system for cardiomyocyte-specific conditional induction of apoptosis.
abstract: Apoptosis is a key determinant of major pathological processes, including chronic cardiac failure. We developed and tested in vitro a novel system to induce cardiomyocyte-specific apoptosis by virus-mediated delivery of a conditional transgene. The entire system was packaged in a lentiviral vector. We used the cardiomyocyte-specific Na(+)-Ca(2+) exchange promoter to control the transcription of the reverse tetracycline transactivator, while the transgene expression was driven by the tetracycline-responsive element. The proapoptotic transgene of choice was the short isoform of the apoptosis-inducing factor, known to quickly induce the caspase-independent apoptosis when overexpressed in cells. Transduction of cardiomyocyte cells with this vector caused a tetracycline-regulated induction of apoptosis, which was not observed in noncardiac cells. Therefore, our system proved a valuable molecular tool for inducing controlled apoptosis in selected cells. Furthermore, the vector we developed is suitable for "lentivirus transgenesis," an interesting strategy recently proposed for the genetic manipulation of animals other than mice, including large mammals.
authors.affiliation: Gruppo Intini-SMA Laboratory of Experimental Cardiology, Institute of Life Sciences, Scuola Superiore Sant'Anna, 56127 Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Agostini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.forename: Marco
authors.initials: M
authors.lastname: Matteucci
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiuppesi
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.forename: Mauro
authors.initials: M
authors.lastname: Pistello
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051033:Apoptosis Inducing Factor / Q000235:genetics*; D002460:Cell Line; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D016086:Lentivirus; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D019831:Sodium-Calcium Exchanger / Q000235:genetics
chemical_list: D051033:Apoptosis Inducing Factor; D019831:Sodium-Calcium Exchanger; D049452:Green Fluorescent Proteins