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

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

Research output: Contribution to journalArticle

Abstract

We investigated the mode of inheritance of susceptibility to nitrogen dioxide (NO2)-induced lung injury in inbred mice. Susceptible C57BL/6J (B6) and resistent C3H/HeJ (C3) mice, as well as F1, 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 (P <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 - Lung Cellular and Molecular Physiology
Volume273
Issue number3 17-3
StatePublished - Sep 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

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Holroyd, K. J., Eleff, S. M., Zhang, L. Y., Jakab, G. J., & Kleeberger, S. R. (1997). Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice. American Journal of Physiology - Lung Cellular and Molecular Physiology, 273(3 17-3).

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

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 273, No. 3 17-3, 09.1997.

Research output: Contribution to journalArticle

Holroyd, Kenneth J. ; Eleff, Scott M. ; Zhang, Liu Yi ; Jakab, George J. ; Kleeberger, Steven R. / Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1997 ; Vol. 273, No. 3 17-3.
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