Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody
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Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody. / Kaczmarek-Hajek, Karina; Zhang, Jiong; Kopp, Robin; Grosche, Antje; Rissiek, Björn; Saul, Anika; Bruzzone, Santina; Engel, Tobias; Jooss, Tina; Krautloher, Anna; Schuster, Stefanie; Magnus, Tim; Stadelmann, Christine; Sirko, Swetlana; Koch-Nolte, Friedrich; Eulenburg, Volker; Nicke, Annette.
in: ELIFE, Jahrgang 7, 03.08.2018, S. e36217.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody
AU - Kaczmarek-Hajek, Karina
AU - Zhang, Jiong
AU - Kopp, Robin
AU - Grosche, Antje
AU - Rissiek, Björn
AU - Saul, Anika
AU - Bruzzone, Santina
AU - Engel, Tobias
AU - Jooss, Tina
AU - Krautloher, Anna
AU - Schuster, Stefanie
AU - Magnus, Tim
AU - Stadelmann, Christine
AU - Sirko, Swetlana
AU - Koch-Nolte, Friedrich
AU - Eulenburg, Volker
AU - Nicke, Annette
N1 - © 2018, Kaczmarek-Hajek et al.
PY - 2018/8/3
Y1 - 2018/8/3
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.7554/eLife.36217
DO - 10.7554/eLife.36217
M3 - SCORING: Journal article
C2 - 30074479
VL - 7
SP - e36217
JO - ELIFE
JF - ELIFE
SN - 2050-084X
ER -