Hypomyelination phenotype caused by impaired differentiation of oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice.

Hypomyelination phenotype caused by impaired differentiation of oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice.
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DOI:
10.1007/s11064-010-0391-0
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发表时间:
2011-07
影响因子:
4.4
通讯作者:
Ohshima, Toshio
Ohshima, Toshio
中科院分区:
医学3区
文献类型:
--
作者:
He, Xiaojuan;Takahashi, Satoru;Suzuki, Hiromi;Hashikawa, Tsutomu;Kulkarni, Ashok B.;Mikoshiba, Katsuhiko;Ohshima, Toshio

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细胞周期蛋白依赖性激酶5 (Cdk5)在神经元迁移和分化以及轴突伸长中起关键作用。虽然已有许多研究分析了Cdk5的神经元功能,但在少突胶质细胞分化过程中也报道了其激酶活性,这表明Cdk5可能在少突胶质细胞中发挥重要作用。在这里,我们描述了在Emx1-cre介导的Cdk5条件敲除(cKO)小鼠(Emx1-cKO)中观察到的一种低髓鞘化表型,其中Cdk5基因在神经元、星形胶质细胞和少突胶质细胞谱系细胞中被删除。相比之下,CaMKII cKO小鼠的Cdk5基因仅在神经元中被删除。由于从少突胶质细胞前体细胞到成熟少突胶质细胞的发育是一个复杂的过程,我们使用少突胶质细胞前体细胞和分化少突胶质细胞的标记物进行了原位杂交。我们的研究结果表明,Emx1-cKO的低髓鞘形成是由于少突胶质细胞分化受损,而不是其前体的增殖或迁移。本研究证实了Cdk5在少突胶质细胞分化中的体内作用。
Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in neuronal migration and differentiation, and in axonal elongation. Although many studies have been conducted to analyze neuronal functions of Cdk5, its kinase activity has also been reported during oligodendrocyte differentiation, which suggests Cdk5 may play an important role in oligodendrocytes. Here, we describe a hypomyelination phenotype observed in Emx1-cre mediated Cdk5 conditional knockout (cKO) mice (Emx1-cKO), in which the Cdk5 gene was deleted in neurons, astrocytes and oligodendrocyte -lineage cells. In contrast, the Cdk5 gene in CaMKII cKO mice was deleted only in neurons. Because the development of mature oligodendrocytes from oligodendrocyte precursor cells is a complex process, we performed in situ hybridization using markers for the oligodendrocyte precursor cell and for the differentiated oligodendrocyte. Our results indicate that hypomyelination in Emx1-cKO is due to the impaired differentiation of oligodendrocytes, rather than to the proliferation or migration of their precursors. The present study confirmed the in vivo role of Cdk5 in oligodendrocyte differentiation.
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