INHERITANCE OF HYPOXIC EXERCISE TOLERANCE IN MICE

All mammals tested, when exposed acutely to a degree of hypoxia above some threshold, exhibit a reduced capacity to perform work. Chronic hy poxic exposure is usually associated with some degree of acclimation r esulting in partial recovery of the preexposure work capacity. The pre sent study reports that, among mice, interindividual variability in re covery of ability to tolerate a standardized hypoxic exercise [t(et); time elapsed in treadmill exercise in hypoxia until 4-s failure to avo id a grid configured to deliver a mild aversive current (0.15 MA)], af ter 8 weeks' exposure to half-atmospheric pressure, is influenced pred ominantly by two unlinked genes of major effect. Two approaches were t aken toward genetic characterization. In one, a maximum-likelihood pro cedure was applied to 11 models of genetic determinacy in the t(et) di stributions of BALB/cBy (C) and C57BL/6By (B6) parental inbred strains , their F-1 hybrid, and the backcross (BC) generations. Breeding tests of the resulting candidate ''best-fit'' major locus inheritance model s involved repeated cycles of selecting, as the progenitor of a new BC generation, the male with the highest value of the test variable in t he previous BC generation, and breeding him to C females. Mice from ea ch of four distinct phenotypes appearing in BC3 were bred to C mice, p roducing distributions expected from two-locus segregation. The second approach was based upon CXB/By RI strain distribution pattern and der ivative breeding tests to reveal phenotypic distributions consistent w ith two-locus inheritance of t(et). Melding these results with a posit ional cloning strategy may permit relating a behavioral difference to specific heritable elements and identifying their products as the (par tial) physiological substrata of the behavior.