Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines.
We established a selection strategy to identify new models for an altered airway inflammatory response from a large compendium of mutant mouse lines that were systemically phenotyped in the German Mouse Clinic (GMC). As selection criteria we included published gene functional data, as well as immuno...
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doaj-eb5e849edd9e468185aae4a588743bdb2020-11-24T21:32:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013450310.1371/journal.pone.0134503Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines.Marion HorschJuan Antonio Aguilar-PimentelClemens BönischChristophe CômeCathrine Kolster-FogKlaus T JensenAnders H LundIcksoo LeeLawrence I GrossmanChristopher SinklerMaik HüttemannErwin BohnHelmut FuchsMarkus OllertValérie Gailus-DurnerMartin Hrabĕ de AngelisJohannes BeckersWe established a selection strategy to identify new models for an altered airway inflammatory response from a large compendium of mutant mouse lines that were systemically phenotyped in the German Mouse Clinic (GMC). As selection criteria we included published gene functional data, as well as immunological and transcriptome data from GMC phenotyping screens under standard conditions. Applying these criteria we identified a few from several hundred mutant mouse lines and further characterized the Cox4i2tm1Hutt, Ifit2tm1.1Ebsb, and Prdm11tm1.1ahl lines following ovalbumin (OVA) sensitization and repeated OVA airway challenge. Challenged Prdm11tm1.1ahl mice exhibited changes in B cell counts, CD4+ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared to the challenged wild type littermates. In contrast, challenged Cox4i2tm1Hutt mutant mice did not show alterations in the humoral or cellular immune response compared to challenged wild type mice. Transcriptome analyses from lungs of the challenged mutant mouse lines showed extensive changes in gene expression in Prdm11tm1.1ahl mice. Functional annotations of regulated genes of all three mutant mouse lines were primarily related to inflammation and airway smooth muscle (ASM) remodeling. We were thus able to define an effective selection strategy to identify new candidate genes for the predisposition to an altered airway inflammatory response under OVA challenge conditions. Similar selection strategies may be used for the analysis of additional genotype-envirotype interactions for other diseases.http://europepmc.org/articles/PMC4532500?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marion Horsch Juan Antonio Aguilar-Pimentel Clemens Bönisch Christophe Côme Cathrine Kolster-Fog Klaus T Jensen Anders H Lund Icksoo Lee Lawrence I Grossman Christopher Sinkler Maik Hüttemann Erwin Bohn Helmut Fuchs Markus Ollert Valérie Gailus-Durner Martin Hrabĕ de Angelis Johannes Beckers |
spellingShingle |
Marion Horsch Juan Antonio Aguilar-Pimentel Clemens Bönisch Christophe Côme Cathrine Kolster-Fog Klaus T Jensen Anders H Lund Icksoo Lee Lawrence I Grossman Christopher Sinkler Maik Hüttemann Erwin Bohn Helmut Fuchs Markus Ollert Valérie Gailus-Durner Martin Hrabĕ de Angelis Johannes Beckers Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. PLoS ONE |
author_facet |
Marion Horsch Juan Antonio Aguilar-Pimentel Clemens Bönisch Christophe Côme Cathrine Kolster-Fog Klaus T Jensen Anders H Lund Icksoo Lee Lawrence I Grossman Christopher Sinkler Maik Hüttemann Erwin Bohn Helmut Fuchs Markus Ollert Valérie Gailus-Durner Martin Hrabĕ de Angelis Johannes Beckers |
author_sort |
Marion Horsch |
title |
Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. |
title_short |
Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. |
title_full |
Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. |
title_fullStr |
Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. |
title_full_unstemmed |
Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. |
title_sort |
cox4i2, ifit2, and prdm11 mutant mice: effective selection of genes predisposing to an altered airway inflammatory response from a large compendium of mutant mouse lines. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
We established a selection strategy to identify new models for an altered airway inflammatory response from a large compendium of mutant mouse lines that were systemically phenotyped in the German Mouse Clinic (GMC). As selection criteria we included published gene functional data, as well as immunological and transcriptome data from GMC phenotyping screens under standard conditions. Applying these criteria we identified a few from several hundred mutant mouse lines and further characterized the Cox4i2tm1Hutt, Ifit2tm1.1Ebsb, and Prdm11tm1.1ahl lines following ovalbumin (OVA) sensitization and repeated OVA airway challenge. Challenged Prdm11tm1.1ahl mice exhibited changes in B cell counts, CD4+ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared to the challenged wild type littermates. In contrast, challenged Cox4i2tm1Hutt mutant mice did not show alterations in the humoral or cellular immune response compared to challenged wild type mice. Transcriptome analyses from lungs of the challenged mutant mouse lines showed extensive changes in gene expression in Prdm11tm1.1ahl mice. Functional annotations of regulated genes of all three mutant mouse lines were primarily related to inflammation and airway smooth muscle (ASM) remodeling. We were thus able to define an effective selection strategy to identify new candidate genes for the predisposition to an altered airway inflammatory response under OVA challenge conditions. Similar selection strategies may be used for the analysis of additional genotype-envirotype interactions for other diseases. |
url |
http://europepmc.org/articles/PMC4532500?pdf=render |
work_keys_str_mv |
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