GENETIC MODEL OF ENDURANCE EXERCISE IN RATS

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DESCRIPTION (Adapted from the applicant's abstract): The long term goal of this work is to identify genes that dictate the difference between low and high endurance performance in mammals. The first step, as presented here, is to develop divergent strains of rats that express to the extremes of endurance running by selective breeding. Two preliminary studies defined parameters for selective breeding for low and high endurance running in rats. First, heritability of treadmill endurance running was estimated in a small test population (n=48) of Sprague-Dawley rats. The distance run until exhaustion was used as a measure of endurance. Two pairs of the highest and lowest were selectively bred. The offspring of the high and low selected rats demonstrated a 29.4 percent difference in running performance in the first generation and had a narrow sense of heritability (h2) of 0.50. Second, the endurance running performance of 192 N/Nih rats was measured for the purpose of selective breeding pairs at the extremes of performance. The N/Nih were chosen because they have wide genetic heterogeneity. Thirteen mating pairs were selected at the extremes of performance and demonstrated a wide selection differential. The 13 high selected females ran on average 3.55 times further than the 13 low selected females. The 13 high selected males ran 5.59 times further than the low males. These data predict a high breeding value for running endurance performance in rats. The specific aims of this work are to: 1. Create strains of low and high endurance performance rats by selective breeding of the N/Nih rats until inheritance plateaus. 2. Continue selection and breeding of the smaller test population of Sprague-Dawley rats until inheritance plateaus. Identification of genes responsible for the differences between low and high exercise endurance would form a broader base for understanding the genetic origins of health and disease. For example, low performance selected rats may concentrate genes that determine the development of heart failure or reduced longevity. In addition, these models of exercise performance could serve as a central component of the proposed "Physiome Project" for functional genomics.