Pathogenomic Mechanisms for Particulate Matter Induction of Acute Lung Injury and Inflammation in Mice

Dr. Leikauf and colleagues at the University of Cincinnati Medical Center hypothesized that the response of mice exposed to high concentrations of inhaled nickel particles was under genetic control. Using nickel, a transition element shown to cause adverse effects at high concentrations in ambient air, the investigators sought to identify the genes involved in controlling the inflammatory and toxic effects of continuous exposure to nickel particles. Leikauf and colleagues evaluated the responses in three mouse strains: in first- generation offspring that resulted from crosses of different strains (F1 mice); in backcross mice—that is, F1 mice crossed with mice of one of the parental strains; and in mice expressing different levels of the human gene for transforming growth factor-α, a factor associated with responses to lung injury. To identify the genes involved in response to nickel, quantitative trait locus (QTL) analysis, haplotype analysis, and microarray technology were used.