Genetic variation in HIF-2α attenuates ventilatory sensitivity and carotid body growth in chronic hypoxia in high-altitude deer mice

We investigated the influence of the high-altitude variant of Epas1 in North American deer mice (Peromyscus maniculatus) on control of breathing and carotid body growth during chronic hypoxia. We created hybrids between high- and low-altitude populations of deer mice (F2 intercross breeding design) to disrupt linkages between genetic loci so physiological effects of Epas1 variants could be examined on an admixed genomic background.

In general, chronic hypoxia (4 weeks at 12 kPa O2) enhanced ventilatory chemosensitivity (assessed as the acute ventilatory response to hypoxic-hypercapnia), increased total ventilation and arterial O2 saturation during progressive poikilocapnic hypoxia, and increased haematocrit and blood haemoglobin content across genotypes. However, effects of chronic hypoxia on ventilatory chemosensitivity were attenuated in mice that were homozygous for the high-altitude Epas1 allele (Epas1H/H).