Telemetry as a tool for developing new rat models

Genetic Models (GMI), based in Indianapolis, Indiana, develops, breeds, and supplies congenic inbred rat models for researchers in medical schools, pharmaceutical companies and other institutions. In particular, GMI specializes in identifying disease mechanisms and establishing drug effectiveness in rat models which mimic human disease syndromes such as diabetes, heart failure, hypertension, obesity and their related complications. Many of the rat models that GMI is developing exhibit hypertension and obesity.

The most promising advances GMI is making are the result of first generation cross breeding of three septe strains of rats that exhibit obesity, congestive heart failure, and diabetes. Offspring from these first generation crosses are characterized by disease profiles, and examination of histologic and physiologic data. These cross breedings have revealed some unexpected characteristics and have resulted in new and unique rat models, an example of which is a brand new strain that exhibits an atherosclerotic lipid profile.

Shortly after the Company was started in 1991, GMI began planning physiological monitoring protocols to characterize their new rat models. Since most of their new models exhibited hypertension, measurement of blood pressure was necessary in order to assess cardiac function. In considering various approaches for monitoring blood pressure, GMI considered tail cuff methodology as well as tethered, indwelling catheters. The tail cuff technique was discarded because it was difficult to obtain physiologically meaningful measurements, especially from obese rats. Use of indwelling catheters was also ruled out due to difficulties in maintaining catheter patency for more than a few weeks.

For GMI, the advent of telemetry in research provided sound solutions to a number of important problems. Compared to alternative techniques, telemetry provided GMI with the ability to do long term, chronic studies of blood pressure profiles. In some cases, only occasional measurements of blood pressure were needed to characterize the model. For example, one of GMI's goals was to develop a model for the study of Syndrome X. In this instance, establishing the presence and magnitude of hypertension at a few time points was sufficient. In other cases, more frequent measurements were needed, as is the case with the SHHF, an inbred strain that is prone to Congestive Heart Failure (CHF). In this model, close tracking of the model through its heart failure profile generally requires weekly if not daily readings. Implantable telemetry also allows GMI to examine differences in daily rhythms between various models and provides a means for examining blood pressure under varying conditions of stress.

GMI's rat model development efforts will be intense and ongoing for the foreseeable future. According to Joe Pesek, one of GMI's founders and President, "DSI's telemetry research system has been very important in confirming the presence of and general characteristics of hypertension in our Zucker Diabetic Fatty (ZDF), a model of NIDDM the Spontaneously Hypertensive Heart Failure (SHHF) rat model, and its ZDF x SHHF (ZSF1) hybrid Atherosclerotic and Nephropathy models."

You can learn more about GMI's efforts to develop new rat models and view telemetered blood pressure data obtained from GMI rat models by accessing their website: http//www.geneticmodels.com/gmi/. For more information contact Joe Pesek at gmi@geneticmodels.com.