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

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

doi:10.1371/journal.pone.0134503

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

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

4 Citations (Scopus)

Abstract

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 Cox4i2^tm1Hutt, Ifit2^tm1.1Ebsb, and Prdm11^tm1.1ahl lines following ovalbumin (OVA) sensitization and repeated OVA airway challenge. Challenged Prdm11^tm1.1ahlmice exhibited changes in B cell counts, CD4⁺ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2^tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared to the challenged wild type lit-termates. In contrast, challenged Cox4i2^tm1Hutt 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 Prdm11^tm1.1ahl 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. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Original language	English
Journal	PLOS ONE
Volume	10
Issue number	8
Pages (from-to)	e0134503
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0134503
Publication status	Published - 11 Aug 2015

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Horsch, M., Aguilar-Pimentel, J. A., Bönisch, C., Côme, C., Kolster-Fog, C., Jensen, K. T., Lund, A. H., Lee, I., Grossman, L. I., Sinkler, C., Hüttemann, M., Bohn, E., Fuchs, H., Ollert, M., Gailus-Durner, V., Hrabĕ de Angelis, M., & Beckers, J. (2015). 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, 10(8), e0134503. https://doi.org/10.1371/journal.pone.0134503

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. / Horsch, Marion; Aguilar-Pimentel, Juan Antonio; Bönisch, Clemens et al.

In: PLOS ONE, Vol. 10, No. 8, 11.08.2015, p. e0134503.

Research output: Contribution to journal › Journal article › Research › peer-review

Horsch, M, Aguilar-Pimentel, JA, Bönisch, C, Côme, C, Kolster-Fog, C, Jensen, KT, Lund, AH, Lee, I, Grossman, LI, Sinkler, C, Hüttemann, M, Bohn, E, Fuchs, H, Ollert, M, Gailus-Durner, V, Hrabĕ de Angelis, M & Beckers, J 2015, '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, vol. 10, no. 8, pp. e0134503. https://doi.org/10.1371/journal.pone.0134503

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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",

abstract = "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 Prdm11tm1.1ahlmice 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 lit-termates. 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. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

author = "Marion Horsch and Aguilar-Pimentel, {Juan Antonio} and Clemens B{\"o}nisch and Christophe C{\^o}me and Cathrine Kolster-Fog and Jensen, {Klaus T} and Lund, {Anders H} and Icksoo Lee and Grossman, {Lawrence I} and Christopher Sinkler and Maik H{\"u}ttemann and Erwin Bohn and Helmut Fuchs and Markus Ollert and Val{\'e}rie Gailus-Durner and {Hrabĕ de Angelis}, Martin and Johannes Beckers",

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T2 - Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines

AU - Horsch, Marion

AU - Aguilar-Pimentel, Juan Antonio

AU - Bönisch, Clemens

AU - Côme, Christophe

AU - Kolster-Fog, Cathrine

AU - Jensen, Klaus T

AU - Lund, Anders H

AU - Lee, Icksoo

AU - Grossman, Lawrence I

AU - Sinkler, Christopher

AU - Hüttemann, Maik

AU - Bohn, Erwin

AU - Fuchs, Helmut

AU - Ollert, Markus

AU - Gailus-Durner, Valérie

AU - Hrabĕ de Angelis, Martin

AU - Beckers, Johannes

PY - 2015/8/11

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N2 - 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 Prdm11tm1.1ahlmice 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 lit-termates. 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. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

AB - 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 Prdm11tm1.1ahlmice 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 lit-termates. 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. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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ER -

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

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