Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination
Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination
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DOI：
10.1038/ng1095
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发表时间：
2003-03-01
期刊：
影响因子：
30.8
通讯作者：
Nave, KA
中科院分区：
文献类型：
--
作者：
Lappe-Siefke, C;Goebbels, S;Nave, KA
少突胶质细胞轴突的髓鞘形成使冲动在中枢神经系统中快速传播。但是轴突和髓鞘之间的长期相互作用却知之甚少。在这里，我们发现编码少突细胞中2',3'-环核苷酸磷酸二酯酶的Cnp1对轴突存活至关重要，但对髓磷脂组装却没有作用。在缺乏胶质环核苷酸磷酸二酯酶的情况下，小鼠整个大脑出现轴突肿胀和神经变性，导致脑积水和过早死亡。但是，与先前研究的髓磷脂突变体不同，这些小鼠的髓磷脂的超微结构、周期性和物理稳定性没有改变。从遗传学上讲，胶质细胞支持轴突完整性的主要功能可以与其维持髓磷脂致密性的功能完全分离。少突胶质细胞功能障碍，如多发性硬化症病变，可能足以引起继发性轴突损失。
Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss.