title: Functional genomics of chlorine-induced acute lung injury in mice.
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.
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 100 Technology Drive, Pittsburgh, PA 15219-3130, USA. gleikauf@pitt.edu
authors.forename: George D
authors.initials: GD
authors.lastname: Leikauf
authors.forename: Hannah
authors.initials: H
authors.lastname: Pope-Varsalona
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Concel
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Liu
authors.forename: Kiflai
authors.initials: K
authors.lastname: Bein
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Brant
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dopico
authors.forename: Y Peter
authors.initials: YP
authors.lastname: Di
authors.forename: An-Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Maggie
authors.initials: M
authors.lastname: Dietsch
authors.forename: Mario
authors.initials: M
authors.lastname: Medvedovic
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Vuga
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Prows
mesh_terms: D000818:Animals; D002713:Chlorine / Q000633:toxicity*; D005260:Female; D005740:Gases / Q000633:toxicity*; D020022:Genetic Predisposition to Disease; D023281:Genomics; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects*; D008171:Lung Diseases / Q000139:chemically induced* / Q000235:genetics* / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal
chemical_list: D005740:Gases; D002713:Chlorine