Functional genomics of chlorine-induced acute lung injury in mice.
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.
Leikauf
George D
GD
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
Pope-Varsalona
Hannah
H
Concel
Vincent J
VJ
Liu
Pengyuan
P
Bein
Kiflai
K
Brant
Kelly A
KA
Dopico
Richard A
RA
Di
Y Peter
YP
Jang
An-Soo
AS
Dietsch
Maggie
M
Medvedovic
Mario
M
Li
Qian
Q
Vuga
Louis J
LJ
Kaminski
Naftali
N
You
Ming
M
Prows
Daniel R
DR
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
D005740:Gases; D002713:Chlorine