Menichella Daniela M, Goodenough Daniel A, Sirkowski Erich, Scherer Steven S, Paul David L
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Neurosci. 2003 Jul 2;23(13):5963-73. doi: 10.1523/JNEUROSCI.23-13-05963.2003.
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.
缝隙连接通道形成蛋白Cx32的突变会导致X连锁型腓骨肌萎缩症，这是一种外周神经系统的脱髓鞘疾病。然而，尽管少突胶质细胞表达Cx32，但中枢髓鞘形成并未受到影响。为了探究这种差异，我们寻找了其他少突胶质细胞连接蛋白。我们发现了Cx47，它特异性地在少突胶质细胞中表达，与髓鞘基因平行调节，并且在少突胶质细胞中与Cx32部分共定位。缺乏Cx47或Cx32的小鼠能够存活。然而，同时缺乏这两种连接蛋白的动物在出生后第6周时会因中枢髓鞘的严重异常而死亡，其特征为髓鞘变薄或缺失、空泡化、轴突周围环扩大、少突胶质细胞死亡以及轴突损失。这些数据首次证明缝隙连接通讯对于正常的中枢髓鞘形成至关重要。
