Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi A B, Seitanidou T, Babinet C, Charnay P
Unité 368 de l'Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, Paris, France.
Nature. 1994 Oct 27;371(6500):796-9. doi: 10.1038/371796a0.
The molecular mechanisms controlling the process of myelination by Schwann cells remain elusive, despite recent progress in the identification and characterization of genes encoding myelin components (reviewed in ref. 1). We have created a null allele in the mouse Krox-20 gene, which encodes a zinc-finger transcription factor, by in-frame insertion of the Escherichia coli lacZ gene, and have shown that hindbrain segmentation is affected in Krox-20-/- embryos. We demonstrate here that Krox-20 is also activated in Schwann cells before the onset of myelination and that its disruption blocks Schwann cells at an early stage in their differentiation, thus preventing myelination in the peripheral nervous system. In Krox-20-/- mice, Schwann cells wrap their cytoplasmic processes only one and a half turns around the axon, and although they express the early myelin marker, myelin-associated glycoprotein, late myelin gene products are absent, including those for protein zero and myelin basic protein. Therefore Krox-20 is likely to control a set of genes required for completion of myelination in the peripheral nervous system.
尽管在编码髓磷脂成分的基因的鉴定和表征方面取得了最新进展（参考文献1中有综述），但控制施万细胞髓鞘形成过程的分子机制仍然不清楚。我们通过在小鼠Krox-20基因（该基因编码一种锌指转录因子）中框内插入大肠杆菌lacZ基因，创建了一个无效等位基因，并表明后脑节段化在Krox-20基因敲除胚胎中受到影响。我们在此证明，Krox-20在髓鞘形成开始前也在施万细胞中被激活，并且其破坏在施万细胞分化的早期阶段阻止了它们，从而防止了周围神经系统中的髓鞘形成。在Krox-20基因敲除小鼠中，施万细胞仅将其细胞质突起围绕轴突缠绕一圈半，并且尽管它们表达早期髓鞘标记物髓鞘相关糖蛋白，但晚期髓鞘基因产物不存在，包括零蛋白和髓鞘碱性蛋白的基因产物。因此，Krox-20可能控制周围神经系统中髓鞘形成完成所需的一组基因。
