title: Genetic mechanisms of susceptibility to oxidative lung injury in mice.
abstract: Genetic background is a known predisposing risk factor for many acute and chronic pulmonary disorders and responses to environmental oxidants. Variation in lung injury responses to oxidative stimuli such as ozone, particles, hyperoxia, and chemotherapeutic agents between genetically standardized inbred mouse strains has been demonstrated. In this review, we discuss quantitative trait loci (QTLs) which contain candidate genes that confer differential susceptibility to oxidative stimuli between strains in mouse models of airway toxicity and disease. We addressed multiple inflammatory, immunity, and antioxidant genes identified as candidate genetic determinants following these strategies, which include tumor necrosis factor (Tnf), toll-like receptor 4 (Tlr4), and the transcription factor NF-E2, related factor 2 (Nrf2). Mice with targeted deletion of these and related genes have provided initial proof of concept for their importance in the respective models. Interestingly, a few regions of the genome appear to have important roles in determining susceptibility to a number of stimuli which may suggest common genetic mechanisms in mice. Though more complete examination of functional association is required, results have potential implications for the role of these candidate genes in the pathogenesis of human pulmonary diseases including asthma, acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and emphysema.
authors.affiliation: Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. cho2@niehs.nih.gov
authors.forename: Hye-Youn
authors.initials: HY
authors.lastname: Cho
authors.forename: Steven R
authors.initials: SR
authors.lastname: Kleeberger
mesh_terms: D000818:Animals; D001483:Base Sequence; D020022:Genetic Predisposition to Disease; D008171:Lung Diseases / Q000235:genetics*; D051379:Mice; D018384:Oxidative Stress; D013045:Species Specificity