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室腔扩大与足细胞钙黏蛋白基因的全神经元消融相关。

Ventricular enlargement associated with the panneural ablation of the podocalyxin gene.

机构信息

Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.

出版信息

Mol Cell Neurosci. 2010 Jan;43(1):90-7. doi: 10.1016/j.mcn.2009.09.011. Epub 2009 Oct 23.

Abstract

Podocalyxin (Podxl) is a type I membrane mucin-protein of the CD34 family abundantly expressed in kidney epithelial cells (podocytes) where it plays a crucial functional role. Podxl is also expressed in tissues other than kidney, like in brain, but its function is ignored. To investigate the functional role of podocalyxin (Podxl) in brain we produced the specific brain-ablation of the Podxl gen in mice by crossing Podxl(floxed/floxed) mice, generated in our laboratory, to mice with pan-neural expression of recombinase Cre (Cre3). Podxl(-/-) mice show no apparent behavioral phenotype but their brains showed enlargement of ventricular volumes detected in vivo by MR imaging. The pattern of brain vasculature was of normal appearance but the thickness of the main carotid artery was significantly increased. Moreover, the histological analysis showed increased number of choroidal capillaries lining the ventricular spaces. These findings are analyzed in the light of the role likely played by podocalyxin in cell migration and cell-cell recognition during brain development and also on the consistent findings of increased ventricular spaces in human pathological disorders like schizophrenia.

摘要

足细胞蛋白(Podocalyxin,Podxl)是一种丰富表达于肾脏上皮细胞(足细胞)的 CD34 家族 I 型膜粘蛋白,在其中发挥着至关重要的功能作用。Podxl 也在肾脏以外的组织中表达,如在大脑中,但它的功能却被忽视了。为了研究足细胞蛋白(Podxl)在大脑中的功能作用,我们通过将实验室中产生的 Podxl(floxed/floxed)小鼠与具有广泛神经元表达 Cre 重组酶(Cre3)的小鼠进行杂交,从而特异性地在大脑中敲除了 Podxl 基因。Podxl(-/-)小鼠没有表现出明显的行为表型,但它们的大脑在体内通过磁共振成像检测到脑室容积增大。脑脉管系统的形态正常,但主要颈动脉的厚度显著增加。此外,组织学分析显示,沿脑室排列的脉络丛毛细血管数量增加。这些发现与 Podxl 在大脑发育过程中可能发挥的细胞迁移和细胞间识别作用有关,也与精神分裂症等人类病理性疾病中脑室空间增大的一致发现有关。

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