Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse

Academic Article


  • The mutations responsible for several human neurodegenerative disorders are expansions of translated CAG repeats beyond a normal size range. To address the role of repeat context, we have introduced a 146 unit CAG repeat into the mouse hypoxanthine phosphoribosyltransferase gene (Hprt). Mutant mice express a form of the HPRT protein that contains a long polyglutamine repeat. These mice develop a phenotype similar to the human translated CAG repeat disorders. Repeat containing mice show a late onset neurological phenotype that progresses to premature death. Neuronal intranuclear inclusions are present in affected mice. Our results show that CAG repeats do not need to be located within one of the classic repeat disorder genes to have a neurotoxic effect.
  • Authors

    Published In

  • Cell  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 11165140
  • Author List

  • Ordway JM; Tallaksen-Greene S; Gutekunst CA; Bernstein EM; Cearley JA; Wiener HW; Dure IV LS; Lindsey R; Hersch SM; Jope RS
  • Start Page

  • 753
  • End Page

  • 763
  • Volume

  • 91
  • Issue

  • 6