Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice

Kenneth J. Holroyd, Scott M. Eleff, Liu Y I Zhang, George J. Jakab, Steven R. Kleeberger

Research output: Contribution to journalArticle

Abstract

We investigated the mode of inheri-tance of susceptibility to nitrogen dioxide (NO2)-induced lung injury in inbred mice. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) mice, as well as FI; F2, and backcross (BX) populations derived from them, were exposed to 15 parts per million NO2 for 3 h. Six hours after exposure, animals were lavaged, and differential cell counts and cell viability (cytotoxicity) were measured. Statistically significant CP <0.05) differences in numbers of lavageable macrophages, epithelial cells, and dead cells were found between inbred strains. Distributions of cellular responses in F1 progeny overlapped both progenitors, and mean responses were intermediate. In C3:BX progeny, ranges of responses to NO2 closely resembled C3 mice, and means were not significantly different between populations. Ranges of cellular responses to NO2 in B6:BX and intercross progeny overlapped both progenitors; mean responses of both populations were intermediate to progenitors. Segregation analyses tested goodness of fit of phenotyping data with various inheritance models, and the highest likelihood for each cell response to NO2 was for the hypothesis two-unlinked loci general. We conclude that there are likely two major unlinked genes that account for differential susceptibility to acute NO2 exposure. The chromosomal location of the genes is not known.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume273
Issue number3 PART 1
StatePublished - 1997

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Nitrogen Dioxide
Lung Injury
Genetic Predisposition to Disease
Inbred C3H Mouse
Population
Genes
Cell Survival
Cell Count
Epithelial Cells
Macrophages

Keywords

  • Air pollution
  • Gene
  • Inbred strains
  • Locus
  • Segregation analysis

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Holroyd, K. J., Eleff, S. M., Zhang, L. Y. I., Jakab, G. J., & Kleeberger, S. R. (1997). Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice. American Journal of Physiology - Gastrointestinal and Liver Physiology, 273(3 PART 1).

Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice. / Holroyd, Kenneth J.; Eleff, Scott M.; Zhang, Liu Y I; Jakab, George J.; Kleeberger, Steven R.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 273, No. 3 PART 1, 1997.

Research output: Contribution to journalArticle

Holroyd, Kenneth J. ; Eleff, Scott M. ; Zhang, Liu Y I ; Jakab, George J. ; Kleeberger, Steven R. / Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1997 ; Vol. 273, No. 3 PART 1.
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