Strategies of Conditional Gene Expression in Myocardium: An Overview

The use of specialized reporter genes to monitor real-time, tissue-specific transgene expression in animal models offers an opportunity to circumvent current limitations associated with the establishment of transgenic mouse mod els. The Cre-loxP and the tetracycline (Tet)-inducible systems are useful meth ods of conditional gene expression that allow spatial (cell-type-specific) and temporal (inducer-dependent) control. Most often, the α-myosin heavy chain (α-MHC) promoter is used in these inducible systems to restrict expression of reporter genes and transgenes to the myocardium. An overview of each induc ible system is described, along with suggested reporter genes for real-time, noninvasive imaging in the myocardium. Effective gene delivery of the induc ible gene expression system is carried out by lentiviral vectors, which offer high transduction efficiency, long-term transgene expression, and low immunogenicity. This chapter outlines the packaging of myocardium-specific in ducible expression systems into lentiviral vectors, in which a transgene and a reporter gene are transduced into cardiomyocytes. In doing so, transgene and reporter expression can be monitored/tracked with bioluminescence imaging (BLI) and positron emission tomography (PET).