Hypertension, Vol 22, 608-617, Copyright © 1993 by American Heart Association
JJ Hunter, H Zhu, KJ Lee, S Kubalak and KR Chien
Transgenic techniques, which allow the introduction of exogenous genes into
the genome of experimental animals, promise to bridge the gap between the
in vitro observations made by molecular and cellular biologists on cardiac
and vascular cells in tissue culture and the physiology and pathology of
the whole organ system. One such application of these techniques is tissue
targeting: by genetic manipulation to direct expression of a protein--such
as a signaling peptide, a growth factor receptor, or an oncogene involved
in cell growth--to a tissue where it normally would not be expressed (or
where expression is tightly controlled) by fusing it to the transcriptional
control sequences of another gene normally expressed in that tissue. In the
cardiovascular system, regulatory sequences for cardiomyocyte- specific
proteins, vascular endothelium-specific proteins, and smooth
muscle-specific proteins can be used to target heterologous genes to their
respective tissues in transgenic animals. The effects that such
perturbations have on organ physiology and intracellular and intercellular
communication can be observed by applying established physiological and
molecular approaches. In this review, we highlight some tissue-specific
genes from cardiac and vascular cell types whose regulatory sequences may
be used to target heterologous proteins; we discuss neutral "reporter"
proteins and signal transduction components as paradigms for the
application of this technique; and we briefly touch on the potentials and
pitfalls of transgenic approaches to molecular physiology.
ARTICLES
Targeting gene expression to specific cardiovascular cell types in transgenic mice
Department of Medicine, University of California, San Diego, School of Medicine, La Jolla 92093-0613.
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