Connexins are critical for normal myelination in the CNS
Connexins are critical for normal myelination in the CNS
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DOI：
10.1523/jneurosci.23-13-05963.2003
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发表时间：
2003-07-02
影响因子：
5.3
通讯作者：
Paul, DL
中科院分区：
文献类型：
--
作者：
Menichella, DM;Goodenough, DA;Paul, DL
缝隙连接通道形成蛋白Cx32的突变导致X连锁的Charcot-Marie-Tooth病，这是一种周围神经系统的脱髓鞘疾病。然而，尽管少突胶质细胞表达Cx32，但中枢髓鞘形成不受影响。为了探索这种差异，我们寻找了更多的少突胶质细胞连接蛋白。我们发现，在少突胶质细胞中特异表达的Cx47与髓鞘基因平行调控，并与Cx32部分共存于少突胶质细胞中。缺乏Cx47或Cx32的小鼠是可以存活的。然而，缺乏这两种连接蛋白的动物在出生后6周死于中央髓鞘的严重异常，其特征是髓鞘变薄或缺失，空泡化，轴突周围环增大，少突胶质细胞死亡和轴突丢失。这些数据提供了第一个证据，证明缝隙连接通讯对正常的中央髓鞘形成至关重要。
Mutations in Cx32, a gap-junction channel-forming protein, result in X-linked Charcot-Marie-Tooth disease, a demyelinating disease of the peripheral nervous system. However, although oligodendrocytes express Cx32, central myelination is unaffected. To explore this discrepancy, we searched for additional oligodendrocyte connexins. We found Cx47, which is expressed specifically in oligodendrocytes, regulated in parallel with myelin genes and partially colocalized with Cx32 in oligodendrocytes. Mice lacking either Cx47 or Cx32 are viable. However, animals lacking both connexins die by postnatal week 6 from profound abnormalities in central myelin, characterized by thin or absent myelin sheaths, vacuolation, enlarged periaxonal collars, oligodendrocyte cell death, and axonal loss. These data provide the first evidence that gap-junction communication is crucial for normal central myelination.