Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice

Cell. 1998 Oct 2;95(1):41-53. doi: 10.1016/s0092-8674(00)81781-x.


Transgenic mice carrying the spinocerebellar ataxia type 1 (SCA1) gene, a polyglutamine neurodegenerative disorder, develop ataxia with ataxin-1 localized to aggregates within cerebellar Purkinje cells nuclei. To examine the importance of nuclear localization and aggregation in pathogenesis, mice expressing ataxin-1[82] with a mutated NLS were established. These mice did not develop disease, demonstrating that nuclear localization is critical for pathogenesis. In a second series of transgenic mice, ataxin-1[77] containing a deletion within the self-association region was expressed within Purkinje cells nuclei. These mice developed ataxia and Purkinje cell pathology similar to the original SCA1 mice. However, no evidence of nuclear ataxin-1 aggregates was found. Thus, although nuclear localization of ataxin-1 is necessary, nuclear aggregation of ataxin-1 is not required to initiate pathogenesis in transgenic mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ataxia / chemically induced
  • Ataxia / metabolism*
  • Ataxin-1
  • Ataxins
  • COS Cells
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Neurodegenerative Diseases / etiology
  • Nuclear Localization Signals / genetics
  • Nuclear Localization Signals / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology
  • Peptides
  • Purkinje Cells / metabolism


  • Ataxin-1
  • Ataxins
  • Atxn1 protein, mouse
  • Nerve Tissue Proteins
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Peptides
  • polyglutamine