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Updated: Jun 17, 2026
Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
Published on: August 25, 2017
Identification of novel susceptibility genes in ozone-induced inflammation in mice
A K Bauer1, E L Travis, S S Malhotra
1Dept of Pathobiology and Diagnostic Investigation Center for Integrative Toxicology B43 Food Safety and Toxicology Bldg, Michigan State University, East Lansing, MI 48824, USA. akbauer@msu.edu
Abstract:
Ozone (O(3)) remains a prevalent air pollutant and public health concern. Inf2 is a significant quantitative trait locus on murine chromosome 17 that contributes to susceptibility to O(3)-induced infiltration of polymorphonuclear leukocytes (PMNs) into the lung, but the mechanisms of susceptibility remain unclear. The study objectives were to confirm and restrict Inf2, and to identify and test novel candidate susceptibility gene(s). Congenic strains of mice that contained overlapping regions of Inf2 and their controls, and mice deficient in either major histocompatibility complex (MHC) class II genes or the Tnf cluster, were exposed to air or O(3). Lung inflammation and gene expression were assessed. Inf2 was restricted from 16.42 Mbp to 0.96 Mbp, and bioinformatic analysis identified MHC class II, the Tnf cluster and other genes in this region that contain potentially informative single nucleotide polymorphisms between the susceptible and resistant mice. Furthermore, O(3)-induced inflammation was significantly reduced in mice deficient in MHC class II genes or the Tnf cluster genes, compared with wild-type controls. Gene expression differences were also observed in MHC class II and Tnf cluster genes. This integrative genetic analysis of Inf2 led to identification of novel O(3) susceptibility genes that may provide important, new therapeutic targets in susceptible individuals.
Insights
Ozone exposure causes lung inflammation. Researchers identified new genes, including MHC class II and Tnf cluster genes, that influence susceptibility to ozone-induced lung inflammation in mice.
Area of Science:
- Environmental Health
- Immunology
- Genetics
Background:
- Ozone (O3) is a common air pollutant posing public health risks.
- Inf2 on mouse chromosome 17 influences susceptibility to O3-induced lung inflammation.
- Mechanisms underlying this susceptibility are not fully understood.
Purpose of the Study:
- To confirm and narrow down the Inf2 locus.
- To identify and evaluate novel candidate genes contributing to O3 susceptibility.
- To elucidate the genetic basis of O3-induced lung inflammation.
Main Methods:
- Congenic mouse strains with overlapping Inf2 regions were used.
- Mice deficient in major histocompatibility complex (MHC) class II or Tnf cluster genes were studied.
- Mice were exposed to filtered air or O3, followed by assessment of lung inflammation and gene expression.
Main Results:
- The Inf2 locus was refined to a 0.96 Mbp region.
- Bioinformatic analysis highlighted MHC class II and Tnf cluster genes within Inf2.
- Mice lacking MHC class II or Tnf cluster genes showed reduced O3-induced lung inflammation.
- Differential gene expression was observed in MHC class II and Tnf cluster genes.
Conclusions:
- Integrative genetic analysis successfully identified novel O3 susceptibility genes.
- MHC class II and Tnf cluster genes play a significant role in O3-induced lung inflammation.
- These identified genes represent potential therapeutic targets for individuals susceptible to O3 exposure.
