Analysis of gene expression and functional characterization of XPR1: a pathogenic gene for primary familial brain calcification
Analysis of gene expression and functional characterization of XPR1: a pathogenic gene for primary familial brain calcification
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原发性家族性脑钙化致病基因 XPR1 的基因表达和功能特征分析
DOI：
10.1007/s00441-017-2663-3
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Chen Wan-Jin
中科院分区：
文献类型：
--
作者：
Yao Xiang-Ping;Zhao Miao;Wang Chong;Guo Xing-Xing;Su Hui-Zhen;Dong En-lin;Chen Hai-Ting;Lai Jin-Hui;Liu Yao-Bin;Wang Ning;Chen Wan-Jin
原发性家族性脑钙化（PFBC）是一种以双侧脑钙化为特征的神经精神疾病，伴有多种神经或精神症状。最近，XPR1变异解释了PFBC作为另一个新的致病基因。然而，XPR 1的分布、基本功能及其与其他三个PFBC致病基因（SLC20A2、PDGFRB和PDGFB）的相互作用尚不清楚。本研究的目的是进一步阐明XPR 1在PFBC脑病理学中的作用。结果，基因表达谱显示XPR1 mRNA在整个小鼠脑中广泛表达。PFBC中最常见的小脑和纹状体含有比其他大脑区域更高水平的XPR1蛋白。此外，XPR1缺陷严重影响Pi外排，XPR1突变似乎通过单倍不足机制产生影响。免疫沉淀和免疫组织化学研究表明XPR 1可以与PDGFRB相互作用，并可能在细胞膜上形成复合物。这些结果表明，XPR 1在维持脑细胞磷酸盐平衡中发挥着重要作用。这为我们理解PFBC的病理生理学提供了一个新的视角。表达网络和与已知致病基因的相互作用可以为PFBC的其他候选基因提供新的线索。
Primary familial brain calcification (PFBC) is a neuropsychiatric disorder characterized by bilateral cerebral calcification with diverse neurologic or psychiatric symptoms. Recently, XPR1 variation has accounted for PFBC as another new causative gene. However, little is known about the distribution and basic function of XPR1 and its interaction with the other three pathogenic genes for PFBC (SLC20A2, PDGFRB and PDGFB). The aim of this study was to further clarify the role of XPR1 in PFBC brain pathology. As a result, gene expression profiles showed that XPR1 mRNA was widely expressed throughout the mouse brain. Cerebellum and striatum, most commonly affected in PFBC, contained a higher level of XPR1 protein than other brain regions. Additionally, XPR1 deficiency seriously affected Pi efflux and XPR1 mutations seemed to have an effect through haploinsufficiency mechanism. The immunoprecipitation and immunohistochemical studies demonstrated that XPR1 could interact with PDGFRB and might form a complex on the cell membrane. These results suggested that XPR1 played a fundamental role in the maintenance of cellular phosphate balance in the brain. This provided us with a novel perspective on understanding the pathophysiology of PFBC. The expression networks and interaction with the known pathogenic genes could shed new light on additional candidate genes for PFBC.
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影响因子：
3.7
作者：
Vanlandewijck M;Lebouvier T;Andaloussi Mäe M;Nahar K;Hornemann S;Kenkel D;Cunha SI;Lennartsson J;Boss A;Heldin CH;Keller A;Betsholtz C
通讯作者：
Betsholtz C
影响因子：
5.3
作者：
Arts FA;Velghe AI;Stevens M;Renauld JC;Essaghir A;Demoulin JB
通讯作者：
Demoulin JB
影响因子：
30.8
作者：
Keller, Annika;Westenberger, Ana;Oliveira, Joao R. M.
通讯作者：
Oliveira, Joao R. M.
影响因子：
12.7
作者：
Miklossy, J;Mackenzie, IR;McGeer, PL
通讯作者：
McGeer, PL
影响因子：
6
作者：
Anheim, Mathieu;Lopez-Sanchez, Uriel;Nicolas, Gael
通讯作者：
Nicolas, Gael