Silencing of the Charcot-Marie-Tooth associated MTMR2 gene decreases proliferation and enhances cell death in primary cultures of Schwann cells.
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.
Chojnowski
Alexandre
A
UMR 679 INSERM (formely U289)-Université Pierre et Marie Curie, IFR70, Faculté de Médecine Pierre et Marie Curie, Paris, France. chojnows@ccr.jussieu.fr
Ravisé
Nicole
N
Bachelin
Corinne
C
Depienne
Christel
C
Ruberg
Merle
M
Brugg
Bernard
B
Laporte
Jocelyn
J
Baron-Van Evercooren
Anne
A
LeGuern
Eric
E
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020868:Gene Silencing; D009186:Myelin Sheath / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D034622:RNA Interference; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology
D016895:Culture Media, Serum-Free; C520716:MTMR2 protein, rat; C498717:Mtmr2 protein, mouse; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D020169:Caspases