Revista Española de Cardiología Revista Española de Cardiología
Rev Esp Cardiol. 2001;54:764-89 - Vol. 54 Núm.06

Genetically modified animal models in cardiovascular research

Florence Dalloz a, Hanna Osinka a, Jeffrey Robbins a

a Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children´s Hospital Research Foundation, Cincinnati OH 45229-3039

Resumen

It is a basic tenet of molecular and clinical medicine that specific protein complements underlie cell and organ function. Since cellular and ultimately organ function depend upon the polypeptides that are present, it is not surprising that when function is altered changes in the protein pools occur. In the heart, numerous examples of contractile protein changes correlate with functional alterations, both during normal development and during the development of numerous pathologies. Similarly, different congenital heart diseases are characterized by certain shifts in the motor proteins. To understand these relationships, and to establish models in which the pathogenic processes can be studied longitudinally, it is necessary to direct the heart to stably synthesize, in the absence of other pleiotropic changes, the candidate protein. Subsequently, one can determine if the protein's presence causes the effects directly or indirectly with the goal being to define potential therapeutic targets. By affecting the heart's protein complement in a defined manner, one has the means to establish both mechanism and the function of the different mutated proteins or protein isoforms. Gene targeting and transgenesis in the mouse provides a means to modify the mammalian genome and the cardiac motor protein complement. By directing expression of an engineered protein to the heart, one is now able to effectively remodel the cardiac protein profile and study the consequences of a single genetic manipulation at the molecular, biochemical, cytological and physiologic levels, both under normal and stress stimuli.

0300-8932/© 2001 Sociedad Española de Cardiología. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

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