Murine Phenotype Analyses and the Role of TRPV1 in Hypoxia

Abstract

The environment in which animals are maintained is a factor that has the potential to alter the physiologic phenotype. We addressed the hypothesis that the standard animal care (SAC) environment cause significant deviations in the circadian variation of heart rate (HR), body temperature (Tb) and activity (ACT) in chronically instrumented mice. These data were used to inform the design of a subsequent study addressing the hypothesis that loss of transient receptor potential vanilloid 1 (TRPV1) function blunts the thermoregulatory, ventilatory and metabolic responses to hypoxia. Mice were implanted with intraperitoneal transmitters for chronic recording of HR, Tb and ACT. The animal environment study consisted of a 3-week protocol comprised of SAC (wk 1) utilizing standard animal care procedures of a health check and bottle and cage changes SPA (service personnel absent; wk 2) with no SAC interventions and building malfunction (BLDMAL+SAC, wk 3). Mean HR was elevated across the week of SAC, as well as for the light and dark cycles. Cage change caused the most profound changes (lasting 4 h), while health check/bottle change alterations lasted approx. 30 min. TRPV1-/- and TRPV1+/+ (wild-type, WT) mice exposed acutely to hypoxia (FIO2=0.1 for 4 h) resulted in a greater hypometabolic response for the mutant compared with WT genotype, reaching a lower value for HR, Tb, ACT, V ̇CO2 (carbon dioxide production) and ventilation. We conclude that the animal care environment provides a novel environment to assess murine phenotype and must be considered in genotype/phenotype assessments. Further, TRPV1 provides a significant tonic input to the integrated thermoregulatory, metabolic and ventilatory responses to hypoxia.