Functional genomics of chlorine-induced acute lung injury in mice

Proc Am Thorac Soc. 2010 Jul;7(4):294-6. doi: 10.1513/pats.201001-005SM.

Abstract

Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chlorine / toxicity*
  • Female
  • Gases / toxicity*
  • Genetic Predisposition to Disease
  • Genomics*
  • Inhalation Exposure
  • Lung / drug effects*
  • Lung Diseases / chemically induced*
  • Lung Diseases / genetics*
  • Lung Diseases / prevention & control
  • Mice
  • Mice, Inbred Strains
  • Models, Animal

Substances

  • Gases
  • Chlorine