Silencing of the CMT associated MTM2 gene decreases proliferation and enhances c

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Neurobiol Dis. 2007 Jan 25

Silencing of the Charcot-Marie-Tooth associated MTMR2 gene decreases

proliferation and enhances cell death in primary cultures of Schwann

cells.

Chojnowski A, Ravise N, Bachelin C, Depienne C, Ruberg M, Brugg B,

Laporte J, Baron-Van Evercooren A, Leguern E.

UMR 679 INSERM (formely U289)-Universite Pierre et Marie Curie,

IFR70, Faculte de Medecine Pierre et Marie Curie, Paris, France.

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.