Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation

Stephen W. Davies, Mark Turmaine, Barbara A. Cozens, Marian DiFiglia, Alan H. Sharp, Christopher A. Ross, Eberhard Scherzinger, Erich E. Wanker, Laura Mangiarini, Gillian P. Bates

Research output: Contribution to journalArticle

Abstract

Huntington's disease (HD) is one of an increasing number of human neurodegenerative disorders caused by a CAG/polyglutamine-repeat expansion. The mutation occurs in a gene of unknown function that is expressed in a wide range of tissues. The molecular mechanism responsible for the delayed onset, selective pattern of neuropathology, and cell death observed in HD has not been described. We have observed that mice transgenic for exon 1 of the human HD gene carrying (CAG)115 to (CAG)156 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype. The appearance in transgenic mice of these inclusions, followed by characteristic morphological change within neuronal nuclei, is strikingly similar to nuclear abnormalities observed in biopsy material from HD patients.

Original languageEnglish (US)
Pages (from-to)537-548
Number of pages12
JournalCell
Volume90
Issue number3
DOIs
StatePublished - Aug 8 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Davies, S. W., Turmaine, M., Cozens, B. A., DiFiglia, M., Sharp, A. H., Ross, C. A., Scherzinger, E., Wanker, E. E., Mangiarini, L., & Bates, G. P. (1997). Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90(3), 537-548. https://doi.org/10.1016/S0092-8674(00)80513-9