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在小鼠大脑发育过程中,对神经发育障碍相关基因 POGZ 的表达分析。

Expression Analyses of POGZ, A Responsible Gene for Neurodevelopmental Disorders, during Mouse Brain Development.

机构信息

Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai, Japan.

Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai, Japan,

出版信息

Dev Neurosci. 2019;41(1-2):139-148. doi: 10.1159/000502128. Epub 2019 Aug 20.

DOI:10.1159/000502128
PMID:31430754
Abstract

POGZ is a heterochromatin protein 1 α-binding protein and regulates gene expression. On the other hand, accumulating pieces of evidence indicate that the POGZ gene abnormalities are involved in various neurodevelopmental disorders. In this study, we prepared a specific antibody against POGZ, anti-POGZ, and carried out biochemical and morphological characterization with mouse brain tissues. Western blotting analyses revealed that POGZ is expressed strongly at embryonic day 13 and then gradually decreased throughout the brain development process. In immunohistochemical analyses, POGZ was found to be enriched in cerebrocortical and hippocampal neurons in the early developmental stage. The nuclear expression was also detected in Purkinje cells in cerebellum at postnatal day (P)7 and P15 but disappeared at P30. In primary cultured hippocampal neurons, while POGZ was distributed mainly in the nucleus, it was also visualized in axon and dendrites with partial localization at synapses in consistency with the results obtained in biochemical fractionation analyses. The obtained results suggest that POGZ takes part in the regulation of synaptic function as well as gene expression during brain development.

摘要

POGZ 是异染色质蛋白 1α 的结合蛋白,可调节基因表达。另一方面,越来越多的证据表明 POGZ 基因异常与多种神经发育障碍有关。在这项研究中,我们制备了针对 POGZ 的特异性抗体(抗 POGZ),并用小鼠脑组织进行了生化和形态学特征分析。Western blot 分析显示,POGZ 在胚胎第 13 天表达强烈,然后在整个大脑发育过程中逐渐减少。在免疫组织化学分析中,POGZ 被发现富集在早期发育阶段的大脑皮质和海马神经元中。在出生后第 7 天(P7)和第 15 天(P15)的小脑浦肯野细胞中也检测到核表达,但在第 30 天(P30)消失。在原代培养的海马神经元中,POGZ 主要分布在核内,但也在轴突和树突中可视化,部分定位于突触,与生化分级分析的结果一致。这些结果表明,POGZ 参与了大脑发育过程中突触功能和基因表达的调节。

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