The Stanford Murine Phenotyping Core

The purpose of the physiologic phenotyping core laboratory is to provide investigators at Stanford the resources to establish precise cardiovascular and metabolic phenotypes for their genetically altered animals. Progress in our ability to manipulate the mammalian genome has led to the proliferation of genetically altered models of cardiovascular disease. Although genetic alteration is possible in any species, the mouse and rat have been the most often used because of their well-defined genetic backgrounds, ease of genetic manipulation, and relatively low costs. In addition, experience in targeted gene disruption (gene knockouts) is most highly developed in the murine model. The Stanford Murine Cardiovascular Phenotyping Core Facility was established in 1994 for two purposes: first, to develop new methods for studying in vivo cardiovascular and metabolic physiology in the mouse and second, to support Stanford investigators in performing physiologic studies in rodent models.

The technical difficulty involved in instrumenting mice combined with the high cost of the equipment involved justified the development of a core facility. Furthermore, mice exhibit a very high degree of variability in cardiovascular parameters depending on their strain, sex, state of arousal and the manner in which the data is obtained. The best opportunity for obtaining quality physiologic data therefore rests with the expertise provided by a single core facility. The presence of this core laboratory is also a major added value for Stanford investigators in competing for NIH grants and initiatives.

The Phenotyping Core has also been a valuable resource for the development of new physiologic monitoring techniques in the murine model and for expanding our knowledge of normal murine physiology. Over the past 15 years, a select group of laboratories, including ours, have adapted physiologic monitoring techniques used previously in larger animals to the murine model. There have been major advances in micro-instrumentation that have made this type of evaluation possible. However, one potential drawback to many of these studies is that most had to be performed under the influence of anesthesia and/or restraint. Given the substantial effects of anesthesia on cardiovascular and metabolic parameters, it was likely that anesthetic agents could mask important physiologic phenotypes in some cases and yield false positive results in others. The Phenotyping Core has pioneered the adaptation of chronic non-anesthetized physiologic monitoring techniques, previously established as a superior methodology in larger animals, to the murine model. We have performed the necessary background studies by establishing baseline data for different murine strains, evaluated the cardiovascular and metabolic responses to anesthesia and restraint, determined normal murine pharmacokinetics, and established one of the nation’s leading laboratories for evaluation of murine cardiovascular responses. Since 1994, we have trained dozens of fellows, students, and research assistants and associates in the latest murine physiologic techniques.