GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16364897

From GONUTS
Jump to: navigation, search
Citation

Goodchild, RE, Kim, CE and Dauer, WT (2005) Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelope. Neuron 48:923-32

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 (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.

Links

PubMed Online version:10.1016/j.neuron.2005.11.010

Keywords

Animals; Brain/abnormalities; Brain/metabolism; Brain/physiopathology; Carrier Proteins/metabolism; Cell Differentiation/genetics; Cell Movement/genetics; Cells, Cultured; Disease Models, Animal; Dystonia Musculorum Deformans/genetics; Dystonia Musculorum Deformans/metabolism; Dystonia Musculorum Deformans/physiopathology; Genetic Predisposition to Disease/genetics; HSC70 Heat-Shock Proteins/metabolism; Membrane Proteins/metabolism; Mice; Mice, Knockout; Mice, Transgenic; Microscopy, Electron, Transmission; Molecular Chaperones/genetics; Mutation/genetics; Neurons/metabolism; Neurons/pathology; Neurons/ultrastructure; Nuclear Envelope/metabolism; Nuclear Envelope/pathology; Nuclear Envelope/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:LMNB1

located_in

GO:0005635: nuclear envelope

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000540)

Seeded From UniProt

complete

MOUSE:LMNB2

located_in

GO:0005635: nuclear envelope

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000540)

Seeded From UniProt

complete

MOUSE:TOR1A

acts_upstream_of_or_within

GO:0006998: nuclear envelope organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3623421
MGI:MGI:3623422

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:TOR1A

acts_upstream_of_or_within

GO:0006998: nuclear envelope organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3623421
MGI:MGI:3623422

P

occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:LMNB1

part_of

GO:0005635: nuclear envelope

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000540)

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.