Identification and localization of ataxin-7 in brain and retina of a patient with cerebellar ataxia type II using anti-peptide antibody

Brain Res Mol Brain Res. 1999 Dec 10;74(1-2):35-43. doi: 10.1016/s0169-328x(99)00256-9.

Abstract

Autosomal dominant cerebellar ataxias (ADCAs) are a complex group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. The spinocerebellar ataxia type 7 (SCA7) is associated with pigmentary macular dystrophy and retinal degeneration leading to blindness caused by a CAG/polyglutamine (polyGln) expansion in the coding region of the SCA7 gene/protein. The SCA7 gene codes for ataxin-7, a protein of unknown function. To investigate its cellular and subcellular localization, we have developed a sequence-specific polyclonal antibody against the N-terminal part of the protein. Immunohistochemical analysis indicated that ataxin-7 accumulates as single nuclear inclusion (NI) in the cells of the brain and retina of a SCA7 patient but not of controls. The 1C2 antibody, directed against expanded polyGln, confirmed the aggregation of mutant ataxin-7 in these NIs. Furthermore, ubiquitin was found in these aggregates, suggesting that mutant ataxin-7 is a target for ubiquitin-dependent proteolysis, but resistant to removal. Electron microscopic studies using immunogold labeling showed that ataxin-7 immunoreactive NIs appear as dense aggregates containing a mixture of granular and filamentary structures. Together, these data confirm the presence of NIs in brain and retina of a SCA7 patient, a common characteristic of disorders caused by expanded CAG/polyGln repeats.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Ataxin-7
  • Brain Chemistry
  • Cerebellar Ataxia / immunology
  • Cerebellar Ataxia / metabolism*
  • Cerebellar Ataxia / pathology
  • Child, Preschool
  • Fatal Outcome
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • Nerve Tissue Proteins / analysis*
  • Nerve Tissue Proteins / immunology
  • Pons / chemistry*
  • Retina / chemistry*
  • Retina / ultrastructure

Substances

  • ATXN7 protein, human
  • Antibodies, Monoclonal
  • Ataxin-7
  • Nerve Tissue Proteins