RGD Reference Report - Modification of Mecp2 dosage alters axonal transport through the Huntingtin/Hap1 pathway. - Rat Genome Database

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Modification of Mecp2 dosage alters axonal transport through the Huntingtin/Hap1 pathway.

Authors: Roux, Jean-Christophe  Zala, Diana  Panayotis, Nicolas  Borges-Correia, Ana  Saudou, Frédéric  Villard, Laurent 
Citation: Roux JC, etal., Neurobiol Dis. 2012 Feb;45(2):786-95. doi: 10.1016/j.nbd.2011.11.002. Epub 2011 Nov 15.
RGD ID: 12790715
Pubmed: PMID:22127389   (View Abstract at PubMed)
DOI: DOI:10.1016/j.nbd.2011.11.002   (Journal Full-text)

Mecp2 deficiency or overexpression causes a wide spectrum of neurological diseases in humans among which Rett Syndrome is the prototype. Pathogenic mechanisms are thought to involve transcriptional deregulation of target genes such as Bdnf together with defects in the general transcriptional program of affected cells. Here we found that two master genes, Huntingtin (Htt) and huntingtin-associated protein (Hap1), involved in the control of Bdnf axonal transport, are altered in the brain of Mecp2-deficient mice. We also revealed an in vivo defect of Bdnf transport throughout the cortico striatal pathway of Mecp2-deficient animals. We found that the velocity of Bdnf-containing vesicles is reduced in vitro in the Mecp2-deficient axons and this deficit can be rescued by the re-expression of Mecp2. The defect in axonal transport is not restricted to Bdnf since transport of the amyloid precursor protein (App) that is Htt and Hap1-dependent is also altered. Finally, treating Mecp2-deficient mice with cysteamine, a molecule increasing the secretion of Bdnf vesicles, improved the lifespan and reduced motor defects, suggesting a new therapeutic strategy for Rett syndrome.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mecp2Ratpositive regulation of anterograde dense core granule transport  IMP  RGD 
Mecp2Ratpositive regulation of retrograde dense core granule transport  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mecp2  (methyl CpG binding protein 2)

Additional Information