26]Molecular analysis of cardiac muscle diseases based on mouse genetics

Abstract

The chapter discusses the molecular analysis of cardiac muscle diseases based on mouse genetics. The chapter outlines several of the experimental approaches that can be utilized in the analysis of cardiac muscle diseases in transgenic mice. In the past few years, there has been an exponential growth in the application of transgenic and gene-targeted approaches to study the cardiovascular system, as well as in coupling traditional cardiovascular physiological and biochemical analyses to the mouse. The culture of cardiomyocytes from individual hearts of mouse embryos and the use of embryonic stem cell differentiation into embryoid bodies as an in vitro model of cardiogenesis provide the opportunity to address gene regulation during cardiac growth and development. Cardiac hypertrophy is characterized by an increase in cell size and a selective up and down regulation of the expression of different genes. In vitro studies have identified the re-expression of protooncogenes, immediate early genes, and the atrial natriuretic factor (ANF) in ventricular myocytes, following hypertrophic stimuli. A distinct advantage of isolated cardiac myocytes is their usefulness for microinjection experiments to investigate the effects of introducing specific signaling molecules (that is, antibodies, proteins, and so on) and expression vectors into single cells.