BACKGROUND: The laboratory mouse is widely used in preclinical models of bronchopulmonary dysplasia, where lung alveolarization is stunted by exposure of pups to hyperoxia. Whether the diverse genetic backgrounds of different inbred mouse strains impacts lung development in newborn mice exposed to hyperoxia has not been systematically assessed. METHODS: Hyperoxia (85% O2 , 14 days)-induced perturbations to lung alveolarization were assessed by design-based stereology in C57BL/6J, BALB/cJ, FVB/NJ, C3H/HeJ, and DBA/2J inbred mouse strains. The expression of components of the lung antioxidant machinery was assessed by real-time reverse transcriptase polymerase chain reaction and immunoblot. RESULTS: Hyperoxia-reduced lung alveolar density in all five mouse strains to different degrees (C57BL/6J, 64.8%; FVB/NJ, 47.4%; BALB/cJ, 46.4%; DBA/2J, 45.9%; and C3H/HeJ, 35.9%). Hyperoxia caused a 94.5% increase in mean linear intercept in the C57BL/6J strain, whilst the C3H/HeJ strain was the least affected (31.6% increase). In contrast, hyperoxia caused a 65.4% increase in septal thickness in the FVB/NJ strain, where the C57BL/6J strain was the least affected (30.3% increase). The expression of components of the lung antioxidant machinery in response to hyperoxia was strain dependent, with the C57BL/6J strain exhibiting the most dramatic engagement. Baseline expression levels of components of the lung antioxidant systems were different in the five mouse strains studied, under both normoxic and hyperoxic conditions. CONCLUSION: The genetic background of laboratory mouse strains dramatically influenced the response of the developing lung to hyperoxic insult. This might be explained, at least in part, by differences in how antioxidant systems are engaged by different mouse strains after hyperoxia exposure.
- Tiono, J.
- Surate Solaligue, D. E.
- Mizikova, I.
- Nardiello, C.
- Vadasz, I.
- Bottcher-Friebertshauser, E.
- Ehrhardt, H.
- Herold, S.
- Seeger, W.
- Morty, R. E.
Keywords
- Animals
- Animals, Newborn
- Bronchopulmonary Dysplasia/*etiology/genetics/metabolism
- Female
- Genetic Background
- Hyperoxia/*complications/genetics
- Lung/*growth & development/metabolism
- Male
- Mice, Inbred Strains
- Oxygen/metabolism
- *alveolarization
- *bronchopulmonary dysplasia
- *hyperoxia
- *strain