PDCD10, the gene mutated in cerebral cavernous malformation 3, is expressed in the neurovascular unit
PDCD10, the gene mutated in cerebral cavernous malformation 3, is expressed in the neurovascular unit
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DOI：
10.1227/01.neu.0000318179.02912.ca
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发表时间：
2008-04-01
期刊：
影响因子：
4.8
通讯作者：
Gunel, Murat
中科院分区：
文献类型：
--
作者：
Tanriover, Gamze;Boylan, Arianne J.;Gunel, Murat
目的：程序性细胞死亡10基因PDCD 10的突变导致常染色体显性遗传家族性脑海绵状血管畸形3（CCM 3）。鲜为人知的是，这个基因在疾病pathogenicity.METHODS的功能：作为第一步，我们分析了信使核糖核酸（mRNA）的表达CCM 3在胚胎和出生后的小鼠脑原位杂交。我们产生和特点CCM 3特异性多克隆抗体和分析CCM 3蛋白表达在人脑和实体器官（脑外）tissues.RESULTS：在胚胎小鼠脑，CCM 3 mRNA被认为是在心室，室下，和中间区，皮质板，发展中的隔膜，纹状体，中脑，脑桥，小脑，和髓质。在出生后的小鼠脑中，我们检测到CCM 3/PDCD 10在嗅球，新皮质，纹状体，隔核，海马，齿状回，丘脑和下丘脑核，下丘，浦肯野和颗粒细胞层和小脑的深核，并在许多细胞和延髓的核中的表达。与CCM 1和CCM 2类似，CCM 3/PDCD 10蛋白在神经血管单位中表达，但在皮质、皮质下和脑干组织内的静脉结构中表达较弱。结论：CCM 3/PDCD 10在多器官系统中的表达模式与CCM 1、CCM 2相似，在脑外组织中动脉内皮细胞表达较强，静脉内皮细胞表达较弱或不表达。PDCD 10/CCM 3在神经血管单位和多器官系统（包括脑）内结构的动脉内皮中高度表达。这些数据提供了关于CCM 3表达及其在病变发展和发病机制中的作用的额外信息。
OBJECTIVE: Mutations in the programmed cell death 10 gene, PDCD10, cause the autosomal-dominant familial cerebral cavernous malformation 3 (CCM3). Little is known about the function of this gene in disease pathogenesis.METHODS: As a first step, we analyzed the messenger ribonucleic acid (mRNA) expression of CCM3 in the embryonic and postnatal mouse brain by in situ hybridization. We generated and characterized CCM3-specific polyclonal antibodies and analyzed CCM3 protein expression in human cerebral and solid organ (extracerebral) tissues using immunohistochemistry.RESULTS: In embryonic mouse brain, CCM3 mRNA is seen in the ventricular, subventricular, and intermediate zones, the cortical plate, the developing septum, striatum, midbrain, pons, cerebellum, and medulla. In the postnatal mouse brain, we detected CCM3/PDCD10 expression in the olfactory bulb, neocortex, striatum, septal nuclei, hippocampus, dentate gyrus, thalamic and hypothalamic nuclei, inferior colliculus, Purkinje and granule cell layers and deep nuclei of the cerebellum, and in many cells and nuclei in the medulla. Similar to CCM1 and CCM2, the CCM3/PDCD10 protein is expressed in the neurovascular unit but weakly in venous structures within cortical, subcortical, and brainstem tissue. CCM3/PDCD10 protein is strongly expressed in arterial endothelium but weakly or not at all in venous endothelium of extracerebral tissue.CONCLUSION: The expression pattern of CCM3/PDCD10 in multiple organ systems displays similarities to CCM1 and CCM2. PDCD10/CCM3 is highly expressed in the neurovascular unit and in the arterial endothelium of structures within multiple organ systems, including the brain. These data provide additional information about CCM3 expression and its role in lesion development and pathogenesis.