Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA

P. Hemachandra Reddy, Maya Williams, Vinod Charles, Lisa Garrett, Lisa Pike-Buchanan, William O. Whetsell, Georgina Miller, Danilo A. Tagle

    Research output: Contribution to journalArticle

    338 Scopus citations

    Abstract

    Huntington disease (HD) is an adult-onset, autosomal dominant inherited human neurodegenerative disorder characterized by hyperkinetic involuntary movements, including motor restlessness and chorea, slowing of voluntary movements and cognitive impairment. Selective regional neuron loss and gliosis in striatum, cerebral cortex, thalamus, subthalamus and hippocampus1-4 are well recognized as neuropathological correlates for the clinical manifestations of HD. The underlying genetic mutation is the expansion of CAG trinucleotide repeats (coding for polyglutamines) to 36-121 copies in exon 1 of the HD genes5-8. The HD mRNA and protein product (huntingtin) show wide spread distribution9-11, and thus much remains to be under stood about the selective and progressive neurodegeneration in HD. To create an experimental animal model for HD, transgenic mice were generated showing widespread expression of full length human HD cDNA with either 16, 48 or 89 CAG repeats. Only mice with 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction with neuron loss and gliosis in striatum, cerebral cortex, thalamus and hippocampus. These animals represent clinically relevant models for HD pathogene sis, and may provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.

    Original languageEnglish (US)
    Pages (from-to)198-202
    Number of pages5
    JournalNature genetics
    Volume20
    Issue number2
    DOIs
    StatePublished - Oct 15 1998

    ASJC Scopus subject areas

    • Genetics

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    Hemachandra Reddy, P., Williams, M., Charles, V., Garrett, L., Pike-Buchanan, L., Whetsell, W. O., Miller, G., & Tagle, D. A. (1998). Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nature genetics, 20(2), 198-202. https://doi.org/10.1038/2510