Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice

Steven R. Kleeberger, Roy C. Levitt, Liu Yi Zhang, Malinda Longphre, Jack Harkema, Anne Jedlicka, Scott M. Eleff, Deborah DiSilvestre, Kenneth J. Holroyd

Research output: Contribution to journalArticle

Abstract

Exposures to the common air pollutant ozone (O3) cause decrements in pulmonary function and induce airway inflammation that is characterized by infiltration of polymorphonuclear neutrophils (PMNs; refs 1-4). Because of the impact that O3 may have on public health, it is critical to identify susceptibility factors. Highly reproducible, significant inter-individual variations in human pulmonary function responses to O3 support the hypothesis that genetic background is an important determinant. Initial analysis of PMN responses to O3 exposure in segregant populations derived from inflammation-prone (susceptible) C57BL/6J (B6) and inflammation- resistant C3H/HeJ (C3) inbred mice indicated that susceptibility was controlled by a locus we termed Inf2 (ref. 7). Subsequent analyses with recombinant inbred strains suggested that a more complex interaction of genes is involved. In this report, we identify a quantitative trait locus (QTL) for O3 susceptibility on chromosome 17. Candidate genes for the locus include Tnf, the gene encoding the prop-inflammatory cytokine tumour necrosis factorα (Tnf). Antibody neutralization of the protein product of this putative candidate germ significantly protected against O3 injury in susceptible mice. These results strongly support linkage of O3 susceptibility to a QTL on chromosome 17 and Tnf as a candidate gene.

Original languageEnglish (US)
Pages (from-to)475-478
Number of pages4
JournalNature genetics
Volume17
Issue number4
DOIs
StatePublished - Jan 1 1997

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ASJC Scopus subject areas

  • Genetics

Cite this

Kleeberger, S. R., Levitt, R. C., Zhang, L. Y., Longphre, M., Harkema, J., Jedlicka, A., Eleff, S. M., DiSilvestre, D., & Holroyd, K. J. (1997). Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice. Nature genetics, 17(4), 475-478. https://doi.org/10.1038/ng1297-475