Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington's disease

Vladimir V. Senatorov, Vinod Charles, P. H. Reddy, Dan A. Tagle, De Maw Chuang

    Research output: Contribution to journalArticlepeer-review

    60 Scopus citations

    Abstract

    Huntington's disease is due to an expansion of CAG repeats in the huntingtin gene. Huntingtin interacts with several proteins including glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We performed immunohistochemical analysis of GAPDH expression in the brains of transgenic mice carrying the huntingtin gene with 89 CAG repeats. In all wild-type animals examined, GAPDH was evenly distributed among the different cell types throughout the brain. In contrast, the majority of transgenic mice showed GAPDH overexpression, with the most prominent GAPDH changes observed in the caudate putamen, globus pallidus, neocortex, and hippocampal formation. Double staining for NeuN and GFAP revealed that GAPDH overexpression occurred exclusively in neurons. Nissl staining analysis of the neocortex and caudate putamen indicated 24 and 27% of cell loss in transgenic mice, respectively. Subcellular fluorescence analysis revealed a predominant increase in GAPDH immunostaining in the nucleus. Thus, we conclude that mutation of huntingtin is associated with GAPDH overexpression and nuclear translocation in discrete populations of brain neurons.

    Original languageEnglish (US)
    Pages (from-to)285-297
    Number of pages13
    JournalMolecular and Cellular Neuroscience
    Volume22
    Issue number3
    DOIs
    StatePublished - Mar 1 2003

    ASJC Scopus subject areas

    • Molecular Biology
    • Cellular and Molecular Neuroscience
    • Cell Biology

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