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

Alexandre Chojnowski; Nicole Ravisé; Corinne Bachelin; Christel Depienne; Merle Ruberg; Bernard Brugg; Jocelyn Laporte; Anne Baron-Van Evercooren; Eric LeGuern

doi:10.1016/j.nbd.2006.12.018

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

Neurobiol Dis. 2007 May;26(2):323-31. doi: 10.1016/j.nbd.2006.12.018. Epub 2007 Jan 25.

Authors

Alexandre Chojnowski¹, Nicole Ravisé, Corinne Bachelin, Christel Depienne, Merle Ruberg, Bernard Brugg, Jocelyn Laporte, Anne Baron-Van Evercooren, Eric LeGuern

Affiliation

¹ UMR 679 INSERM (formely U289)-Université Pierre et Marie Curie, IFR70, Faculté de Médecine Pierre et Marie Curie, Paris, France. [email protected]

PMID: 17336078
DOI: 10.1016/j.nbd.2006.12.018

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Apoptosis / drug effects
Apoptosis / genetics
Caspases / metabolism
Cell Death / drug effects
Cell Death / genetics
Cell Proliferation
Cells, Cultured
Charcot-Marie-Tooth Disease / genetics*
Charcot-Marie-Tooth Disease / metabolism
Charcot-Marie-Tooth Disease / physiopathology
Culture Media, Serum-Free / pharmacology
Down-Regulation / drug effects
Down-Regulation / genetics
Gene Expression Profiling
Gene Expression Regulation, Developmental / genetics
Gene Silencing*
Myelin Sheath / genetics*
Myelin Sheath / metabolism
Myelin Sheath / pathology
Peripheral Nerves / metabolism*
Peripheral Nerves / pathology
Peripheral Nerves / physiopathology
Protein Tyrosine Phosphatases / genetics*
Protein Tyrosine Phosphatases, Non-Receptor
RNA Interference
Rats
Schwann Cells / metabolism*
Schwann Cells / pathology

Substances

Culture Media, Serum-Free
MTMR2 protein, rat
Mtmr2 protein, mouse
Protein Tyrosine Phosphatases
Protein Tyrosine Phosphatases, Non-Receptor
Caspases