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Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion
Microglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a G(αi)-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1(CreERT2) mic...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281947/ https://www.ncbi.nlm.nih.gov/pubmed/32513210 http://dx.doi.org/10.1186/s13041-020-00630-4 |
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author | Lee, Younghwan Lee, Ji-Won Nam, Hyeri Yu, Seong-Woon |
author_facet | Lee, Younghwan Lee, Ji-Won Nam, Hyeri Yu, Seong-Woon |
author_sort | Lee, Younghwan |
collection | PubMed |
description | Microglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a G(αi)-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1(CreERT2) mice express Cre recombinase in a tamoxifen-inducible manner and have been widely used to delete target genes in microglia, since microglia are long-lived cells and outlive peripheral macrophages, which continuously turn over and lose their gene modification over time. ATG7 is an E1-like enzyme that plays an essential role in two ubiquitin-like reactions, ATG12-ATG5 conjugation and LC3-lipidation in autophagy. To study the role of ATG7 in adult microglia, we generated Cx3cr1(CreERT2):Atg7(fl/fl) mice and deleted Atg7 at the age of 8 weeks, and found induction of intestinal adhesion. Since intestinal adhesion is caused by excessive inflammation, these results suggest that deletion of Atg7 in intestinal macrophages even for a short time results in inflammation that cannot be rescued by replenishment with wild-type intestinal macrophages. Our finding suggests that, depending on the roles of the gene, Cx3cr1-Cre-mediated gene deletion may yield unanticipated physiological outcomes outside the central nervous system, and careful necropsy is necessary to assure the microglia-specific roles of the target gene. |
format | Online Article Text |
id | pubmed-7281947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72819472020-06-09 Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion Lee, Younghwan Lee, Ji-Won Nam, Hyeri Yu, Seong-Woon Mol Brain Micro Report Microglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a G(αi)-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1(CreERT2) mice express Cre recombinase in a tamoxifen-inducible manner and have been widely used to delete target genes in microglia, since microglia are long-lived cells and outlive peripheral macrophages, which continuously turn over and lose their gene modification over time. ATG7 is an E1-like enzyme that plays an essential role in two ubiquitin-like reactions, ATG12-ATG5 conjugation and LC3-lipidation in autophagy. To study the role of ATG7 in adult microglia, we generated Cx3cr1(CreERT2):Atg7(fl/fl) mice and deleted Atg7 at the age of 8 weeks, and found induction of intestinal adhesion. Since intestinal adhesion is caused by excessive inflammation, these results suggest that deletion of Atg7 in intestinal macrophages even for a short time results in inflammation that cannot be rescued by replenishment with wild-type intestinal macrophages. Our finding suggests that, depending on the roles of the gene, Cx3cr1-Cre-mediated gene deletion may yield unanticipated physiological outcomes outside the central nervous system, and careful necropsy is necessary to assure the microglia-specific roles of the target gene. BioMed Central 2020-06-08 /pmc/articles/PMC7281947/ /pubmed/32513210 http://dx.doi.org/10.1186/s13041-020-00630-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Micro Report Lee, Younghwan Lee, Ji-Won Nam, Hyeri Yu, Seong-Woon Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion |
title | Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion |
title_full | Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion |
title_fullStr | Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion |
title_full_unstemmed | Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion |
title_short | Cx3cr1(CreERT2)-driven Atg7 deletion in adult mice induces intestinal adhesion |
title_sort | cx3cr1(creert2)-driven atg7 deletion in adult mice induces intestinal adhesion |
topic | Micro Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281947/ https://www.ncbi.nlm.nih.gov/pubmed/32513210 http://dx.doi.org/10.1186/s13041-020-00630-4 |
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