Transcriptomics

Dataset Information

2

Expression data from a Charcot-Marie-Tooth 1B neuropathy mouse model


ABSTRACT: We have generated mouse models of real CMT1B mutations in the gene encoding for myelin protein zero (P0). One of these mutants, P0S63del is retained in the ER where it elicits an unfolded protein response (UPR). Genetic ablation of the UPR factor CHOP restores the motor capacity in S63del mice. We used microarray to decipher the molecular mechanism undelying the P0S63del neuropathy and the rescue in S63del/Chop null nerves. Sciatic nerves were dissected from WT, S63del, Chop null and S63del/Chop null mice at three different time points: (i) postnatal day 5 (P5) when myelination has just started and only the primary effects of the presence of the mutant protein should be detected; (ii) P28, around the peak of myelination, when all the downstream targets of CHOP should be activated; and (iii) 4 months, to check for secondary effects of the disease and because this was the time-point when the motor and morphological rescue due to the ablation of CHOP were clearly detectable.

ORGANISM(S): Mus musculus  

SUBMITTER: Maurizio D'Antonio   Lawrence Wrabetz 

PROVIDER: E-GEOD-40610 | ArrayExpress | 2013-05-01

SECONDARY ACCESSION(S): GSE40610PRJNA174396

REPOSITORIES: GEO, ArrayExpress

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Publications

Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.

D'Antonio Maurizio M   Musner Nicolò N   Scapin Cristina C   Ungaro Daniela D   Del Carro Ubaldo U   Ron David D   Feltri M Laura ML   Wrabetz Lawrence L  

The Journal of experimental medicine 20130401 4


P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescu  ...[more]

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