Journal Article

Reversal of neuropathy phenotypes in conditional mouse model of Charcot–Marie–Tooth disease type 2E

Florence Dequen, Mohammed Filali, Roxanne C. Larivière, Rodolphe Perrot, Shin-Ichi Hisanaga and Jean-Pierre Julien

in Human Molecular Genetics

Volume 19, issue 13, pages 2616-2629
Published in print July 2010 | ISSN: 0964-6906
Published online April 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq149
Reversal of neuropathy phenotypes in conditional mouse model of Charcot–Marie–Tooth disease type 2E

Show Summary Details

Preview

Mutations in the gene encoding for the neurofilament light subunit (NF-L) are responsible for Charcot–Marie–Tooth (CMT) neuropathy type 2E. To address whether CMT2E disease is potentially reversible, we generated a mouse model with conditional doxycycline-responsive gene system that allows repression of mutant hNF-LP22S transgene expression in adult neurons. The hNF-LP22S;tTa transgenic (tg) mice recapitulated key features of CMT2E disease, including aberrant hindlimb posture, motor deficits, hypertrophy of muscle fibres and loss of muscle innervation without neuronal loss. Remarkably, a 3-month treatment of hNF-LP22S;tTa mice with doxycycline after onset of disease efficiently down-regulated expression of hNF-LP22S and it caused reversal of CMT neurological phenotypes with restoration of muscle innervation and of neurofilament protein distribution along the sciatic nerve. These data suggest that therapeutic approaches aimed at abolishing expression or neutralizing hNF-L mutants might not only halt the progress of CMT2E disease, but also revert the disabilities.

Journal Article.  7822 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.