Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma.

Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma.
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DOI:
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发表时间:
1996-01
期刊:
影响因子:
11.2
通讯作者:
Naoki Yokota;J. Aruga;S. Takai;Kiyomi Yamada;M. Hamazaki;T. Iwase;Haruhiko Sugimura;K. Mikoshiba
Naoki Yokota;J. Aruga;S. Takai;Kiyomi Yamada;M. Hamazaki;T. Iwase;Haruhiko Sugimura;K. Mikoshiba
中科院分区:
医学1区
文献类型:
--
作者:
Naoki Yokota;J. Aruga;S. Takai;Kiyomi Yamada;M. Hamazaki;T. Iwase;Haruhiko Sugimura;K. Mikoshiba

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Zic是一种新的锌指蛋白,在成年和发育中的小鼠小脑中显示高度限制性的表达模式,并且与最近克隆的果蝇配对规则基因Opa高度同源。为了阐明人类小脑发育的机制及其与人类神经系统疾病的关系,我们分离了人Zic cDNA,并利用抗重组Zic蛋白的单克隆抗体检测了其表达。人Zic cDNA与小鼠Zic cDNA的核苷酸序列同源性为85%。其推定的氨基酸序列是高度保守的(> 99%),除了只有两个氨基酸残基的取代。染色体原位杂交将人Zic基因定位于染色体3q 24带。人Zic蛋白在小脑颗粒细胞谱系的细胞核中被免疫化学检测到,从外部胚层的祖细胞到内部颗粒层的后迁移细胞。此外,Zic蛋白在髓母细胞瘤(26/29例)中检测到,而没有其他肿瘤检查(超过70例,包括原始神经外胚层肿瘤)表达这种蛋白。这些发现表明Zic是髓母细胞瘤以及人小脑颗粒细胞谱系的潜在生物标志物。
Zic is a novel zinc finger protein which displays a highly restricted expression pattern in the adult and developing mouse cerebellum and is highly homologous to the recently cloned Drosophila pair-rule gene Opa. To clarify the mechanism for the development of the human cerebellum and its involvement in human nervous system diseases, we have isolated human Zic cDNA and examined its expression by using monoclonal antibody against recombinant Zic protein. The nucleotide sequence of human Zic cDNA is 85% homologous to that of mouse Zic cDNA. Its putative amino acid sequence is highly conserved (> 99%) except for substitution of only two amino acid residues. In situ chromosome hybridization localized the human Zic gene to chromosome band 3q24. Human Zic protein was immunohistochemically detected in the nuclei of the cerebellar granule cell lineage from the progenitor cells of the external germinal layer to the postmigrated cells of the internal granular layer. Furthermore, Zic protein was detected in medulloblastoma (26/29 cases), whereas no other tumors examined (over 70 cases including primitive neuroectodermal tumors) expressed this protein. These findings suggest that Zic is a potential biomarker for medulloblastoma as well as the human cerebellar granule cell lineage.