| First Author | Goodchild RE | Year | 2005 |
| Journal | Neuron | Volume | 48 |
| Issue | 6 | Pages | 923-32 |
| PubMed ID | 16364897 | Mgi Jnum | J:107596 |
| Mgi Id | MGI:3621520 | Doi | 10.1016/j.neuron.2005.11.010 |
| Citation | Goodchild RE, et al. (2005) Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelope. Neuron 48(6):923-32 |
| abstractText | 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. |
