Physiological Genomics
A number of papers submitted in conjunction with the October 2002 NHLBI symposium on mouse cardiovascular phenotyping1 appear in this issue of Physiological Genomics. Researchers at the symposium discussed current technologies, such as advances in imaging and measurements of electrophysiological phenotypes, used to assess mouse models of human cardiovascular disease. Meeting organizer Cecilia Lo has contributed a meeting report (5) detailing highlighted topics.
In a review article, Collins et al. (3) describe the use of Doppler echocardiography to evaluate cardiac phenotypes in transgenic mice. With ultrasound, dimensions and performance of the mouse heart can readily be obtained. Two-dimensional Doppler echocardiography enables scientists to determine cardiac output and to assess cardiac performance of animals with valvular disease. Klaas Kramer and Lewis Kinter (4) describe the use of implanted radiotelemetry devices to record rodent cardiovascular measurements free from the stress-related perturbations that generally accompany human handling of animals. Such implants can be used to record a number of signals, including blood oxygen content, heart rate, and blood pressure. Radio implants also provide researchers with the opportunity to reduce the number of mice or rats used in experiments, since instrumented animals may be "reused" in different studies. Daniel Bernstein (1) reviews exercise testing in mouse models of cardiovascular disease, noting that many transgenic models only evince an altered cardiac phenotype under the stress of exercise. For example, ß1-adrenergic receptor knockout mice have exercise-induced increases in O2 that are identical to wild-type animals, but their heart rate does not increase as much during exercise. For these transgenic mice to maintain a normal
O2, they must have increased left ventricular stroke volume.
Charles Berul (2) describes mouse models of human cardiac arrhythmias and their electrophysiological assessment. Animals may be studied using an ex vivo method with perfused hearts or by using an in vivo method with implantation of subcutaneous electrodes to record electrocardiograms (ECG). Mice may be followed long term via implanted telemetry devices that transmit ECG data at desired intervals. Soufan et al. (6) detail the three-dimensional (3D) reconstruction of gene expression patterns in mouse hearts during cardiac development, a method in which hearts are sectioned, hybridized in situ to a suite of myocardium-specific genes, digitally photographed, and then "reconstructed" using imaging software. By staining sections with probes for other heart-specific mRNAs, it is possible to generate a 3D record of gene expression at a certain time point in development.
These review articles demonstrate the depth of current research into mouse models of cardiovascular disease, which, coupled with the availability of the mouse genome, holds the promise of significant future advances in translational research.
FOOTNOTES
The "NHLBI Symposium on Phenotyping: Mouse Cardiovascular Function and Development" was held at the Natcher Conference Center, NIH, Bethesda, MD, on October 1011, 2002.
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