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

Rose E. Goodchild, Connie Eunji Kim, William T. Dauer

Research output: Contribution to journalArticle

259 Scopus citations

Abstract

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 (Δgag) in the gene encoding torsinA. Here we show that neurons from both torsinA null (Tor1a-/-) and homozygous disease mutant "knockin" mice (Tor1aΔgag/Δgag) 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.

Original languageEnglish (US)
Pages (from-to)923-932
Number of pages10
JournalNeuron
Volume48
Issue number6
DOIs
StatePublished - Dec 22 2005
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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