A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross

Richard Gelinas1,3, Elissa J Chesler2, Daphne Vasconcelos1, Darla R Miller2, Yue Yuan3, Kai Wang3, David Galas1,31Battelle Memorial Institute, Columbus, OH; 2Oak Ridge National Laboratory, Oak Ridge, TN; 3Institute for Systems Biology, Seattle, WA, USAAbstract: The antineoplastic drug bleomycin lead...

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Main Authors: Gelinas R, Chesler EJ, Vasconcelos D, Miller DR, Yuan Y, Wang K, Galas D
Format: Article
Language:English
Published: Dove Medical Press 2011-07-01
Series:Pharmacogenomics and Personalized Medicine
Online Access:http://www.dovepress.com/a-genetic-approach-to-the-prediction-of-drug-side-effects-bleomycin-in-a7800
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spelling doaj-cefd192cafb241dca9aee9e05d773fca2020-11-25T01:50:32ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662011-07-012011default3545A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative crossGelinas RChesler EJVasconcelos DMiller DRYuan YWang KGalas DRichard Gelinas1,3, Elissa J Chesler2, Daphne Vasconcelos1, Darla R Miller2, Yue Yuan3, Kai Wang3, David Galas1,31Battelle Memorial Institute, Columbus, OH; 2Oak Ridge National Laboratory, Oak Ridge, TN; 3Institute for Systems Biology, Seattle, WA, USAAbstract: The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs) were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain.Keywords: collaborative cross, drug side effects, genetic diversity, disease susceptibility, disease resistance, bleomycin, lung diseasehttp://www.dovepress.com/a-genetic-approach-to-the-prediction-of-drug-side-effects-bleomycin-in-a7800
collection DOAJ
language English
format Article
sources DOAJ
author Gelinas R
Chesler EJ
Vasconcelos D
Miller DR
Yuan Y
Wang K
Galas D
spellingShingle Gelinas R
Chesler EJ
Vasconcelos D
Miller DR
Yuan Y
Wang K
Galas D
A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross
Pharmacogenomics and Personalized Medicine
author_facet Gelinas R
Chesler EJ
Vasconcelos D
Miller DR
Yuan Y
Wang K
Galas D
author_sort Gelinas R
title A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross
title_short A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross
title_full A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross
title_fullStr A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross
title_full_unstemmed A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross
title_sort genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross
publisher Dove Medical Press
series Pharmacogenomics and Personalized Medicine
issn 1178-7066
publishDate 2011-07-01
description Richard Gelinas1,3, Elissa J Chesler2, Daphne Vasconcelos1, Darla R Miller2, Yue Yuan3, Kai Wang3, David Galas1,31Battelle Memorial Institute, Columbus, OH; 2Oak Ridge National Laboratory, Oak Ridge, TN; 3Institute for Systems Biology, Seattle, WA, USAAbstract: The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs) were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain.Keywords: collaborative cross, drug side effects, genetic diversity, disease susceptibility, disease resistance, bleomycin, lung disease
url http://www.dovepress.com/a-genetic-approach-to-the-prediction-of-drug-side-effects-bleomycin-in-a7800
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