© 2001 American Heart Association, Inc.
Editorial |
To Cre or Not To Cre
The Next Generation of Mouse Models of Human Cardiac Diseases
From the Institute of Molecular Medicine, University of California San Diego, School of Medicine, La Jolla, Calif.
Correspondence to Kenneth R. Chien MD, PhD, 0613C Basic Science Building, UCSD School of Medicine, La Jolla, CA 92093. E-mail kchien@ucsd.edu
Key Words: transgenic mouse models • heart disease • cardiomyopathy • gene targeting • homologous recombination
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Introduction |
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Connecting genes and molecular pathways with in vivo physiological endpoints has never been a simple task. Dissecting the effects of the causal from the phenomenal, the environmental from the inherited, the developmental from the postnatal, the primary from the secondary, and the polygenic from the monogenic has been confounding at best. For those of us interested in complex human cardiovascular diseases, the situation has been even more difficult, given the multifactorial and integrative nature of the most important human diseases and biological processes, such as angiogenesis, atherogenesis, obesity, hypertension, and heart failure, to name a few. Over the last few years, a movement to capitalize on the availability of genetically modified mouse models has led to a resurgence in integrative physiology that has been spurred on by the development of a host of new technology for assaying in vivo phenotypes in the living mouse that now encompasses conscious blood pressure recording, hemodynamic catheterization, microdigitized angiography, noninvasive imaging via echocardiography, new MRI technology, programmed stimulation, long-term Holter monitoring, microsurgical implementation of pressure overload in both the right and left ventricles, in utero myocyte implantation, and many other new techniques.1 In short, physiologists have reinvented themselves by pushing the limits of miniaturization in genetically modified mouse model systems.
In parallel, molecular biologists have expanded the tool box
for generating genetically modified animals, which now encompasses the
activation of a given mutation in specific cell types and at specific
times using cre-lox technology for conditional
mutagenesis.2 In this regard,
the study in this
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