Acclimatization of low altitude-bred deer mice ( Peromyscus maniculatus) to high altitude

A colony of deer mice subspecies ( Peromyscus maniculatus sonoriensis) native to high altitude (HA) has been maintained at sea level for 18-20 generations and remains genetically unchanged. To determine if these animals retain responsiveness to hypoxia, one group (9-11 wk old) was acclimated to HA (3,800 m) for 8 wk. Age-matched control animals were acclimated to a lower altitude (LA; 252 m). Maximal O₂ uptake (V̇o_2max) was measured at the respective altitudes. On a separate day, lung volume, diffusing capacity for carbon monoxide (DL_CO), and pulmonary blood flow were measured under anesthesia using a rebreathing technique at two inspired O₂ tensions. The HA-acclimated deer mice maintained a normal V̇o_2max relative to LA baseline. Compared with LA control mice, antemortem lung volume was larger in HA mice in a manner dependent on alveolar O₂ tension. Systemic hematocrit, pulmonary blood flow, and standardized DL_CO did not differ significantly between groups. HA mice showed a higher postmortem alveolar-capillary hematocrit, larger alveolar ducts, and smaller distal conducting structures. In HA mice, absolute volumes of alveolar type I epithelia and endothelia were higher whereas that of interstitia was lower than in LA mice. These structural changes occurred without a net increase in whole-lung septal tissue-capillary volumes or surface areas. Thus, deer mice bred and raised to adulthood at LA retain phenotypic plasticity and adapt to HA without a decrement in V̇o_2max via structural (enlarged airspaces, alveolar septal remodeling) and nonstructural (lung expansion under hypoxia) mechanisms and without an increase in systemic hematocrit or compensatory lung growth. NEW & NOTEWORTHY Deer mice ( Peromyscus maniculatus) are robust and very active mammals that are found across the North American continent. They are also highly adaptable to extreme environments. When introduced to high altitude they retain remarkable adaptive ability to the low-oxygen environment via lung expansion and remodeling of existing lung structure, thereby maintaining normal aerobic capacity without generating more red blood cells or additional lung tissue.