Decker Laurence, Desmarquet-Trin-Dinh Carole, Taillebourg Emmanuel, Ghislain Julien, Vallat Jean-Michel, Charnay Patrick
Institut National de la Santé et de la Recherche Médicale, U784, Ecole Normale Supérieure, 75230 Paris Cedex 05, France.
J Neurosci. 2006 Sep 20;26(38):9771-9. doi: 10.1523/JNEUROSCI.0716-06.2006.
Onset of myelination in Schwann cells is governed by several transcription factors, including Krox20/Egr2, and mutations affecting Krox20 result in various human hereditary peripheral neuropathies, including congenital hypomyelinating neuropathy (CHN) and Charcot-Marie-Tooth disease (CMT). Similar molecular information is not available on the process of myelin maintenance. We have generated conditional Krox20 mutations in the mouse that allowed us to develop models for CHN and CMT. In the latter case, specific inactivation of Krox20 in adult Schwann cells results in severe demyelination, involving rapid Schwann cell dedifferentiation and increased proliferation, followed by an attempt to remyelinate and a block at the promyelinating stage. These data establish that Krox20 is not only required for the onset of myelination but that it is also crucial for the maintenance of the myelinating state. Furthermore, myelin maintenance appears as a very dynamic process in which Krox20 may constitute a molecular switch between Schwann cell myelination and demyelination programs.
雪旺细胞髓鞘形成的起始受多种转录因子调控，包括Krox20/Egr2，影响Krox20的突变会导致多种人类遗传性周围神经病，包括先天性髓鞘形成低下性神经病（CHN）和夏科-马里-图斯病（CMT）。关于髓鞘维持过程，尚无类似的分子信息。我们在小鼠中产生了条件性Krox20突变，这使我们能够建立CHN和CMT模型。在后一种情况下，成年雪旺细胞中Krox20的特异性失活会导致严重的脱髓鞘，包括雪旺细胞迅速去分化和增殖增加，随后试图进行髓鞘再生，并在髓鞘形成前期受阻。这些数据表明，Krox20不仅是髓鞘形成起始所必需的，而且对维持髓鞘形成状态也至关重要。此外，髓鞘维持似乎是一个非常动态的过程，其中Krox20可能构成雪旺细胞髓鞘形成和脱髓鞘程序之间的分子开关。
