Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody
The P2X7 channel is involved in the pathogenesis of various CNS diseases. An increasing number of studies suggest its presence in neurons where its putative functions remain controversial for more than a decade. To resolve this issue and to provide a model for analysis of P2X7 functions, we generate...
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doaj-b062997e054c49a3929a6f440c8b1a7e2021-05-05T16:04:06ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.36217Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobodyKarina Kaczmarek-Hajek0Jiong Zhang1Robin Kopp2https://orcid.org/0000-0002-1639-2868Antje Grosche3Björn Rissiek4https://orcid.org/0000-0001-5327-5479Anika Saul5Santina Bruzzone6Tobias Engel7Tina Jooss8Anna Krautloher9Stefanie Schuster10Tim Magnus11Christine Stadelmann12Swetlana Sirko13https://orcid.org/0000-0001-5950-616XFriedrich Koch-Nolte14Volker Eulenburg15https://orcid.org/0000-0002-4878-5746Annette Nicke16https://orcid.org/0000-0001-6798-505XDepartment of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Göttingen, GermanyDepartment of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Göttingen, Germany; Walther Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Munich, GermanyWalther Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Munich, GermanyInstitute for Human Genetics, University of Regensburg, Regensburg, Germany; Department of Physiological Genomics, Ludwig-Maximilians-Universität München, München, GermanyDepartment of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Göttingen, GermanyDepartment of Experimental Medicine and CEBR, University of Genova, Genova, ItalyDepartment of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, IrelandWalther Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Munich, GermanyWalther Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Munich, GermanyInstitute of Biochemistry, University Erlangen-Nürnberg, Erlangen, GermanyDepartment of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuropathology, University Medical Center, Göttingen, GermanyDepartment of Physiological Genomics, Ludwig-Maximilians-Universität München, München, Germany; Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyDepartment of Immunology, University Hospital Hamburg-Eppendorf, Hamburg, GermanyInstitute of Biochemistry, University Erlangen-Nürnberg, Erlangen, Germany; Department of Anaesthesiology and Intensive Care Therapy, University of Leipzig, Leipzig, GermanyDepartment of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Göttingen, Germany; Walther Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Munich, GermanyThe P2X7 channel is involved in the pathogenesis of various CNS diseases. An increasing number of studies suggest its presence in neurons where its putative functions remain controversial for more than a decade. To resolve this issue and to provide a model for analysis of P2X7 functions, we generated P2X7 BAC transgenic mice that allow visualization of functional EGFP-tagged P2X7 receptors in vivo. Extensive characterization of these mice revealed dominant P2X7-EGFP protein expression in microglia, Bergmann glia, and oligodendrocytes, but not in neurons. These findings were further validated by microglia- and oligodendrocyte-specific P2X7 deletion and a novel P2X7-specific nanobody. In addition to the first quantitative analysis of P2X7 protein expression in the CNS, we show potential consequences of its overexpression in ischemic retina and post-traumatic cerebral cortex grey matter. This novel mouse model overcomes previous limitations in P2X7 research and will help to determine its physiological roles and contribution to diseases.https://elifesciences.org/articles/36217purinergic P2X7 receptorBAC transgeneconditional knockoutnanobody |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karina Kaczmarek-Hajek Jiong Zhang Robin Kopp Antje Grosche Björn Rissiek Anika Saul Santina Bruzzone Tobias Engel Tina Jooss Anna Krautloher Stefanie Schuster Tim Magnus Christine Stadelmann Swetlana Sirko Friedrich Koch-Nolte Volker Eulenburg Annette Nicke |
spellingShingle |
Karina Kaczmarek-Hajek Jiong Zhang Robin Kopp Antje Grosche Björn Rissiek Anika Saul Santina Bruzzone Tobias Engel Tina Jooss Anna Krautloher Stefanie Schuster Tim Magnus Christine Stadelmann Swetlana Sirko Friedrich Koch-Nolte Volker Eulenburg Annette Nicke Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody eLife purinergic P2X7 receptor BAC transgene conditional knockout nanobody |
author_facet |
Karina Kaczmarek-Hajek Jiong Zhang Robin Kopp Antje Grosche Björn Rissiek Anika Saul Santina Bruzzone Tobias Engel Tina Jooss Anna Krautloher Stefanie Schuster Tim Magnus Christine Stadelmann Swetlana Sirko Friedrich Koch-Nolte Volker Eulenburg Annette Nicke |
author_sort |
Karina Kaczmarek-Hajek |
title |
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody |
title_short |
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody |
title_full |
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody |
title_fullStr |
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody |
title_full_unstemmed |
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody |
title_sort |
re-evaluation of neuronal p2x7 expression using novel mouse models and a p2x7-specific nanobody |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-08-01 |
description |
The P2X7 channel is involved in the pathogenesis of various CNS diseases. An increasing number of studies suggest its presence in neurons where its putative functions remain controversial for more than a decade. To resolve this issue and to provide a model for analysis of P2X7 functions, we generated P2X7 BAC transgenic mice that allow visualization of functional EGFP-tagged P2X7 receptors in vivo. Extensive characterization of these mice revealed dominant P2X7-EGFP protein expression in microglia, Bergmann glia, and oligodendrocytes, but not in neurons. These findings were further validated by microglia- and oligodendrocyte-specific P2X7 deletion and a novel P2X7-specific nanobody. In addition to the first quantitative analysis of P2X7 protein expression in the CNS, we show potential consequences of its overexpression in ischemic retina and post-traumatic cerebral cortex grey matter. This novel mouse model overcomes previous limitations in P2X7 research and will help to determine its physiological roles and contribution to diseases. |
topic |
purinergic P2X7 receptor BAC transgene conditional knockout nanobody |
url |
https://elifesciences.org/articles/36217 |
work_keys_str_mv |
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