© 1996 American Heart Association, Inc.
Articles |
Conditional Transgene Expression in the Heart
the Section of Molecular Cardiology, Albert Einstein College of Medicine, Bronx, NY (Z.Y., G.I.F.), and Gladstone Institute of Cardiovascular Disease, University of California, San Francisco (C.S.R.).
Correspondence to Glenn I. Fishman, MD, Section of Molecular Cardiology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461. E-mail fishman@aecom.yu.edu.
Conditional transgene expression is a potentially useful approach to investigate complex biological systems in vivo. We recently demonstrated that tetracycline-responsive promoters could be employed to achieve regulated, cardiac-specific expression of target genes in transgenic mice. To more fully define the quantitative and spatial parameters associated with tetracycline-regulated gene expression in the heart, we crossed transgenic mice harboring either a firefly luciferase or a nuclear-localized bacterial lacZ target gene with strains expressing a tetracycline-controlled transactivator (tTA) under the regulatory control of 2.9 kb of 5' flanking sequence from the rat 
-myosin heavy chain gene. Luciferase activity was induced nearly 300-fold in the hearts of binary-transgenic mice compared with mice carrying only the luciferase reporter gene. No significant transactivation was observed in any other tissues examined. Binary transgenics harboring the lacZ reporter gene showed substantial ß-galactosidase activity throughout the heart, but the response of individual cardiac myocytes was heterogeneous. For both reporter genes, tetracycline treatment fully repressed tTA-dependent transactivation. These data provide important insights into the nature of studies that can be successfully addressed using the tetracycline-regulated gene expression system in the heart.
Key Words: conditional • binary • tetracycline • transgenic • heart
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