Genetic Manipulation of the Rabbit Heart via Transgenesis

Abstract

Background —Transgenesis using cardiac-specific expression has been valuable in exploring cardiac structure-function relationships. To date, cardiac-selective studies have been confined to the mouse. However, the utility of the mouse is limited in certain, possibly critical, aspects with respect to cardiovascular function. Methods and Results —To establish the potential validity of transgenic methodology for remodeling a larger mammalian heart, we explored cardiac-selective expression in transgenic rabbits. The murine α- and β-cardiac myosin heavy chain gene promoters were used to express a reporter gene, and transgene expression was quantified in cardiac, skeletal, and smooth muscles as well as in nonmuscle tissues. Although neither promoter exactly mimics endogenous patterns of myosin heavy chain expression, both are able to drive high levels of transgene expression in the cardiac compartment. Neither promoter is active in smooth muscle or nonmuscle tissues. Conclusions —Directed organ-specific expression is feasible in a larger animal with existing reagents, and cardiac-selective transgenic manipulation is possible in the rabbit.