Silencing of the Charcot–Marie–Tooth associated MTMR2 gene decreases proliferation and enhances cell death in primary cultures of Schwann cells

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• 作者：Alex ; re Chojnowski ; Nicole Ravisé ; Corinne Bachelin ; Christel Depienne ; Merle Ruberg ; Bernard Brugg ; Jocelyn Laporte ; Anne Baron-Van Evercooren ; Eric LeGuern
• 关键词：MTMR2 ; Charcot– ; Marie– ; Tooth ; RNAi ; Schwann ; Proliferation ; Apoptosis
• 刊名：Neurobiology of Disease
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：26
• 期：2
• 页码：323-331
• 全文大小：1074 K

文摘

Loss of function of the myotubularin (MTM)-related protein 2 (MTMR2) in Schwann cells causes Charcot–Marie–Tooth disease type 4B1, a severe demyelinating neuropathy, but the consequences of MTMR2 disruption in Schwann cells are unknown. We established the expression profile of MTMR2 by real-time RT-PCR during rat myelination and showed it to be preferentially expressed at the onset of the myelination period. We developed a model in which MTMR2 loss of function was reproduced in primary cultures of Schwann cells by RNA interference. We found that depletion of MTMR2 in Schwann cells decreased their rate of proliferation. Furthermore, when cultivated in serum-free medium, MTMR2 depletion increased the number of Schwann cells that died by a caspase-dependent process. These results support the hypothesis that loss of MTMR2 in patients, by decreasing Schwann cells proliferation and survival, may impair the first stages of myelination of the peripheral nervous system.