The rs1799895 single nucleotide polymorphism (SNP) is a non-synonymous base pair change in SOD3 that results in an arginine-to-glycine substitution (R213G) in extracellular superoxide dismutase protein (EC-SOD). This region is responsible for EC- SODs binding to extracellular matrix increases plasma levels 10-fold. The R213G SNP protects smokers from developing chronic obstructive pulmonary disease (COPD) and acute exacerbations of COPD. The goal of this proposal is to elucidate the mechanism by which the R213G protects the lung from tobacco smoke. To accomplish this aim, we have created a knock-in mouse with the identical SNP. Our methods will utilize more than a decade of experience studying the EC-SOD gene and COPD.