Does lack of gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?

Supplemental oxygen (O) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing () gene expression increases the injurious effects of hyperoxia (Hyp). and C57Bl/6J mice were exposed to 21% O (Air) or 40% O (Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), and and gene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack of expression and further decreased by hyperoxia. expression was increased in Hyp mice and decreased in both groups. On P56d, heme oxygenase-1 was increased by hyperoxia when was absent. There were significantly more immune cells from Hyp groups than from the Air group and a greater proportion of lymphocytes in Hyp mice. expression was significantly decreased in mice; and expression was increased in Hyp mice compared with other groups. Tissue fraction was decreased in Air mice; bronchiolar smooth muscle was decreased in mice. does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression of and in Hyp mice suggests gene redundancy within the model.