Genetic and genomic mechanisms of neonatal hyperoxic lung injury in the inbred mouse

Oxidative stress contributes to the pathogenesis of many respiratory disorders, including bronchopulmonary dysplasia (BPD), or chronic lung disease in infants. Treatment of BPD often involves respiratory support with high oxygen levels, and oxidant injury is an adverse side effect associated with vascular damage and impaired lung development and function in a subset of infants. Differential susceptibility to BPD is poorly understood and previous studies have demonstrated genetic susceptibility to hyperoxic lung injury in strains of adult inbred mice. Furthermore, genetic polymorphisms in a few candidate genes have been associated with BPD in clinical cohorts; however, specific genetic factors predisposing neonates to oxidant lung injury are poorly understood. The objective of this dissertation was to utilize integrated genetic and genomic approaches to identify predictors of susceptibility to neonatal hyperoxic lung injury. Neonates from 36 strains of inbred mice were screened for lungDoctor of Philosoph