Variable susceptibility to cigarette smoke-induced emphysema in 34 inbred strains of mice implicates Abi3bp in emphysema susceptibility

Josiah E. Radder, Alyssa D. Gregory, Adriana S. Leme, Michael H. Cho, Yanxia Chu, Neil J. Kelly, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David Sparrow, Terri H. Beaty, James D. Crapo, Edwin K. Silverman, Yingze Zhang, Annerose Berndt, Steven D. Shapiro

Research output: Contribution to journalArticle

Abstract

Chronic obstructive pulmonary disease (COPD) is caused by a complex interaction of environmental exposures, most commonly cigarette smoke, and genetic factors. Chronic cigarette smoke exposure in the mouse is acommonly used animal model ofCOPD.We aimedto expand our knowledge about the variable susceptibility of inbred strains to this model and test for genetic variants associated with this trait. To that end, we sought to measure differential susceptibility to cigarette smoke-inducedemphysema inthemouse, identify genetic loci associated with this quantitative trait, and find homologous human genes associated with COPD. Alveolar chord length (CL) in 34 inbred strains ofmice was measured after 6 months of exposure to cigarette smoke. After testing for association, we connected amurine candidate locus to a publishedmetaanalysis of moderate-to-severe COPD.We identified deleterious mutations in a candidate gene in silico and measured gene expression in extreme strains. A/J was the most susceptible strain in our survey (D CL 7.0 6 2.2 mm) and CBA/J was the least susceptible (D CL 20.3 6 1.2 mm).By integratingmouse andhumangenome-wide scans,weidentified the candidate gene Abi3bp. CBA/J mice harbor predicted deleterious variants in Abi3bp, and expression of the gene differs significantly between CBA/J and A/J mice. This is the first report of susceptibility to cigarette smoke-induced emphysema in 34 inbred strains of mice, and Abi3bp is identified as a potential contributor to this phenotype.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume57
Issue number3
DOIs
StatePublished - Sep 2017

Keywords

  • Abi3bp
  • Animal model
  • COPD
  • Emphysema

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Radder, J. E., Gregory, A. D., Leme, A. S., Cho, M. H., Chu, Y., Kelly, N. J., Bakke, P., Gulsvik, A., Litonjua, A. A., Sparrow, D., Beaty, T. H., Crapo, J. D., Silverman, E. K., Zhang, Y., Berndt, A., & Shapiro, S. D. (2017). Variable susceptibility to cigarette smoke-induced emphysema in 34 inbred strains of mice implicates Abi3bp in emphysema susceptibility. American journal of respiratory cell and molecular biology, 57(3), 367-375. https://doi.org/10.1165/rcmb.2016-0220OC