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Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelope.

Neuron | Dec 22, 2005

http://www.ncbi.nlm.nih.gov/pubmed/16364897

An enigmatic feature of many genetic diseases is that mutations in widely expressed genes cause tissue-specific illness. One example is DYT1 dystonia, a neurodevelopmental disease caused by an in-frame deletion (Deltagag) in the gene encoding torsinA. Here we show that neurons from both torsinA null (Tor1a(-/-)) and homozygous disease mutant "knockin" mice (Tor1a(Deltagag/Deltagag)) contain severely abnormal nuclear membranes, although non-neuronal cell types appear normal. These membrane abnormalities develop in postmigratory embryonic neurons and subsequently worsen with further neuronal maturation, a finding evocative of the developmental dependence of DYT1 dystonia. These observations demonstrate that neurons have a unique requirement for nuclear envelope localized torsinA function and suggest that loss of this activity is a key molecular event in the pathogenesis of DYT1 dystonia.

Pubmed ID: 16364897 RIS Download

Mesh terms: Animals | Brain | Carrier Proteins | Cell Differentiation | Cell Movement | Cells, Cultured | Disease Models, Animal | Dystonia Musculorum Deformans | Genetic Predisposition to Disease | HSC70 Heat-Shock Proteins | Membrane Proteins | Mice | Mice, Knockout | Mice, Transgenic | Microscopy, Electron, Transmission | Molecular Chaperones | Mutation | Neurons | Nuclear Envelope

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Associated grants

  • Agency: NICHD NIH HHS, Id: R01 HD045708-01A1

Mouse Genome Informatics (Data, Gene Annotation)

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