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Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions

The adenosine A(2A) receptor (A(2A)R), a G protein-coupled receptor, is involved in numerous and varied physiological and pathological processes, including inflammation, immune responses, blood flow, and neurotransmission. Accordingly, it has become an important drug target for the treatment of neur...

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Autores principales: Wang, Muran, Li, Zewen, Song, Yue, Sun, Qiuqin, Deng, Lu, Lin, Zhiqing, Zeng, Yang, Qiu, Chunhong, Lin, Jingjing, Guo, Hui, Chen, Jiangfan, Guo, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434489/
https://www.ncbi.nlm.nih.gov/pubmed/36059431
http://dx.doi.org/10.3389/fnana.2022.978641
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author Wang, Muran
Li, Zewen
Song, Yue
Sun, Qiuqin
Deng, Lu
Lin, Zhiqing
Zeng, Yang
Qiu, Chunhong
Lin, Jingjing
Guo, Hui
Chen, Jiangfan
Guo, Wei
author_facet Wang, Muran
Li, Zewen
Song, Yue
Sun, Qiuqin
Deng, Lu
Lin, Zhiqing
Zeng, Yang
Qiu, Chunhong
Lin, Jingjing
Guo, Hui
Chen, Jiangfan
Guo, Wei
author_sort Wang, Muran
collection PubMed
description The adenosine A(2A) receptor (A(2A)R), a G protein-coupled receptor, is involved in numerous and varied physiological and pathological processes, including inflammation, immune responses, blood flow, and neurotransmission. Accordingly, it has become an important drug target for the treatment of neuropsychiatric disorders. However, the exact brain distribution of A(2A)R in regions outside the striatum that display relatively low levels of endogenous A(2A)R expression has hampered the exploration of A(2A)R functions under both physiological and pathological conditions. To further study the detailed distribution of the A(2A)R in low-expression regions, we have generated A(2A)R knock-in mice in which the 3xHA-2xMyc epitope tag sequence was fused to the C-terminus of A(2A)R (A(2A)R-tag mice) via CRISPR/Cas9 technology. Here, using CRISPR/Cas9 technology, we have generated A(2A)R knock-in mice in which the 3xHA-2xMyc epitope tag sequence was fused to the C-terminus of A(2A)R (A(2A)R-tag mice). The A(2A)R-tag mice exhibited normal locomotor activity and emotional state. Consistent with previous studies, A(2A)R fluorescence was widely detected in the striatum, nucleus accumbens, and olfactory tubercles, with numerous labeled cells being evident in these regions in the A(2A)R-tag mouse. Importantly, we also identified the presence of a few but clearly labeled cells in heterogeneous brain regions where A(2A)R expression has not previously been unambiguously detected, including the lateral septum, hippocampus, amygdala, cerebral cortex, and gigantocellular reticular nucleus. The A(2A)R-tag mouse represents a novel useful genetic tool for monitoring the expression of A(2A)R and dissecting its functions in brain regions other than the striatum.
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spelling pubmed-94344892022-09-02 Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions Wang, Muran Li, Zewen Song, Yue Sun, Qiuqin Deng, Lu Lin, Zhiqing Zeng, Yang Qiu, Chunhong Lin, Jingjing Guo, Hui Chen, Jiangfan Guo, Wei Front Neuroanat Neuroanatomy The adenosine A(2A) receptor (A(2A)R), a G protein-coupled receptor, is involved in numerous and varied physiological and pathological processes, including inflammation, immune responses, blood flow, and neurotransmission. Accordingly, it has become an important drug target for the treatment of neuropsychiatric disorders. However, the exact brain distribution of A(2A)R in regions outside the striatum that display relatively low levels of endogenous A(2A)R expression has hampered the exploration of A(2A)R functions under both physiological and pathological conditions. To further study the detailed distribution of the A(2A)R in low-expression regions, we have generated A(2A)R knock-in mice in which the 3xHA-2xMyc epitope tag sequence was fused to the C-terminus of A(2A)R (A(2A)R-tag mice) via CRISPR/Cas9 technology. Here, using CRISPR/Cas9 technology, we have generated A(2A)R knock-in mice in which the 3xHA-2xMyc epitope tag sequence was fused to the C-terminus of A(2A)R (A(2A)R-tag mice). The A(2A)R-tag mice exhibited normal locomotor activity and emotional state. Consistent with previous studies, A(2A)R fluorescence was widely detected in the striatum, nucleus accumbens, and olfactory tubercles, with numerous labeled cells being evident in these regions in the A(2A)R-tag mouse. Importantly, we also identified the presence of a few but clearly labeled cells in heterogeneous brain regions where A(2A)R expression has not previously been unambiguously detected, including the lateral septum, hippocampus, amygdala, cerebral cortex, and gigantocellular reticular nucleus. The A(2A)R-tag mouse represents a novel useful genetic tool for monitoring the expression of A(2A)R and dissecting its functions in brain regions other than the striatum. Frontiers Media S.A. 2022-08-18 /pmc/articles/PMC9434489/ /pubmed/36059431 http://dx.doi.org/10.3389/fnana.2022.978641 Text en Copyright © 2022 Wang, Li, Song, Sun, Deng, Lin, Zeng, Qiu, Lin, Guo, Chen and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroanatomy
Wang, Muran
Li, Zewen
Song, Yue
Sun, Qiuqin
Deng, Lu
Lin, Zhiqing
Zeng, Yang
Qiu, Chunhong
Lin, Jingjing
Guo, Hui
Chen, Jiangfan
Guo, Wei
Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions
title Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions
title_full Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions
title_fullStr Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions
title_full_unstemmed Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions
title_short Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions
title_sort genetic tagging of the adenosine a2a receptor reveals its heterogeneous expression in brain regions
topic Neuroanatomy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434489/
https://www.ncbi.nlm.nih.gov/pubmed/36059431
http://dx.doi.org/10.3389/fnana.2022.978641
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