Genetic susceptibility to hyperoxic lung injury in mice and the role of heme oxygenase

L. Otterbein, S. M. Eleff, K. J. Holroyd, L. Zhang, Augustine M K Choi , S. R. Kleeberger

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the mechanisms of genetic susceptibility to hyperoxic lung injury in C57BL/6J (susceptible) and C3H/HeJ (resistant) inbred mouse strains. C57BL/6J (B6) and C3H/HeJ (C3) mice, as well as F1, F2, and back-cross populations, were exposed to 100% O2 for 48 hr. Animals were lavaged and total protein content of bronchoalveolar lavage (BAL) returns (a marker of lung permeability) was used as the phenotype of lung injury. A significant (P<0.05) difference in BAL protein was found between inbred strains. Distributions of protein responses in F1 and C3 backcross (C3:BX) mice were similar to C3, and means were not significantly different between populations. Ranges of responses to O2 in B6:BX and F2 progeny overlapped both progenitors and mean responses were intermediate to them. Goodness of fit of phenotype data was tested with 43 segregation models. The highest likelihood for response to O2 was for the hypothesis, mixed general. We also tested whether O2-induced expression of heme oxygenase (HO-1) differs between B6 and C3 mice. O2 caused significantly greater induction of HO-1 mRNA in B6 mice (5-fold) compared to C3 (2-fold). In a population of O2-exposed B6:BX mice, HO-1 mRNA induction cosegregated with total BAL protein (r = 0.716, P<0.05). We conclude that there is likely one major gene that accounts for differential susceptibility to O2 exposure, and that HO-1 is a candidate gene.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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