ParkinsonCanadaV1, France, Analysis, bibRecord, 000217

Modest loss of peripheral axons and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1

Identifieur interne : 000217 ( France/Analysis ); précédent : 000216; suivant : 000218

Modest loss of peripheral axons and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1

Auteurs : Florence Dequen [Canada] ; Pascale Bomont [États-Unis, France] ; Geneviève Gowing [Canada] ; Don W. Cleveland [États-Unis] ; Jean-Pierre Julien [Canada]

Source :

Journal of neurochemistry [ 0022-3042 ] ; 2008.

RBID : PMC:3657508

Abstract

Mutations in gigaxonin are responsible for Giant Axonal Neuropathy (GAN), a progressive neurodegenerative disorder associated with abnormal accumulations of Intermediate Filaments (IFs). Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and TBCB. Here, we report the generation of a mouse model with targeted deletion of Gan exon 1 (Gan^{Δexon1;Δexon1}). Analyses of the Gan^{Δexon1;Δexon1} mice revealed increased levels of various IFs proteins in nervous system and the presence of IFs inclusion bodies in the brain. Despite deficiency of full length gigaxonin, the Gan^{Δexon1;Δexon1} mice do not develop overt neurological phenotypes and giant axons reminiscent of the human GAN disease. We propose that the existence of a short gigaxonin isoform expressed in the spinal cord could underlie the mitigation of GAN-phenotypes in Gan^{Δexon1;Δexon1} mice. Nonetheless, the Gan^{Δexon1;Δexon1} mice exhibited modest increase in axon calibers and 27% axonal loss in the L5 ventral roots. This new mouse model should provide a useful tool for testing potential therapeutic approaches for GAN disease.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657508

DOI: 10.1111/j.1471-4159.2008.05601.x
PubMed: 18680552
PubMed Central: 3657508

Affiliations:

Links to Exploration step

PMC:3657508

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</italic>
 mice. Nonetheless, the <italic>Gan<sup>Δexon1;Δexon1</sup>
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La maladie de Parkinson au Canada (serveur d'exploration)

Modest loss of peripheral axons and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1

Modest loss of peripheral axons and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1

Source :

Abstract

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Links to Exploration step

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Pour générer des pages wiki

	La maladie de Parkinson au Canada (serveur d'exploration)
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