GENETIC-ANALYSIS OF OZONE-INDUCED ACUTE LUNG INJURY IN SENSITIVE AND RESISTANT STRAINS OF MICE

Citation
Dr. Prows et al., GENETIC-ANALYSIS OF OZONE-INDUCED ACUTE LUNG INJURY IN SENSITIVE AND RESISTANT STRAINS OF MICE, Nature genetics, 17(4), 1997, pp. 471-474
Citations number
30
Journal title
ISSN journal
10614036
Volume
17
Issue
4
Year of publication
1997
Pages
471 - 474
Database
ISI
SICI code
1061-4036(1997)17:4<471:GOOALI>2.0.ZU;2-9
Abstract
Epidemiological studies have found air pollution to be associated with excessive mortality, particularly death from respiratory and cardiova scular causes(1,2). Interpretation of these findings is controversial, however, because toxicological mechanisms controlling mortality are u ncertain. Susceptibility to many air pollutants entails an oxidative s tress response(3,4). Accordingly, the best-characterized oxidant air p ollutant is ozone(5), which causes direct oxidative damage of lung bio molecules(6). An underlying characteristic derived from clinical and e pidemiological studies of healthy and asthmatic individuals of all age s is marked variability in the respiratory effects of ozone(7-11). Thi s susceptibility difference among humans suggests that genetic determi nants may control predisposition to the harmful effects of ozone(12). Mice also vary considerably in their response to ozone(13-15), Moreove r, ozone-induced differences in strain responses(16) indicate that sus ceptibility in mice can be genetically determined. Therefore, we used inbred mice to investigate the genetic determinants of acute lung inju ry, Recombinant inbred (RI) strains derived from A/J (A) mice (sensiti ve) and C57BL/6J (B) mice (resistant) showed a continuous phenotypic p attern, suggesting a multigenic trait. Quantitative trait locus and RI analyses suggested three major loci linked to ozone susceptibility. D ifferences in phenotype ratios among the reciprocal backcrosses were c onsistent with parental imprinting, These findings implicate various g enetic and epigenetic factors in individual susceptibility to air poll ution.