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

Vladimir V. Senatorov, Vinod Charles, P (Hemachandra) Reddy, Dan A. Tagle, De Maw Chuang

    Research output: Contribution to journalArticle

    59 Citations (Scopus)

    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

    Fingerprint

    Glyceraldehyde-3-Phosphate Dehydrogenases
    Huntington Disease
    Transgenic Mice
    Putamen
    Neocortex
    Brain
    Staining and Labeling
    Neurons
    Globus Pallidus
    Wild Animals
    Genes
    Hippocampus
    Fluorescence
    Mutation

    ASJC Scopus subject areas

    • Molecular Biology
    • Cellular and Molecular Neuroscience
    • Developmental Neuroscience

    Cite this

    Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington's disease. / Senatorov, Vladimir V.; Charles, Vinod; Reddy, P (Hemachandra); Tagle, Dan A.; Chuang, De Maw.

    In: Molecular and Cellular Neuroscience, Vol. 22, No. 3, 01.03.2003, p. 285-297.

    Research output: Contribution to journalArticle

    Senatorov, Vladimir V. ; Charles, Vinod ; Reddy, P (Hemachandra) ; Tagle, Dan A. ; Chuang, De Maw. / Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington's disease. In: Molecular and Cellular Neuroscience. 2003 ; Vol. 22, No. 3. pp. 285-297.
    @article{d1f176c85de3426f99bc8f7d4e1efbf9,
    title = "Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington's disease",
    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.",
    author = "Senatorov, {Vladimir V.} and Vinod Charles and Reddy, {P (Hemachandra)} and Tagle, {Dan A.} and Chuang, {De Maw}",
    year = "2003",
    month = "3",
    day = "1",
    doi = "10.1016/S1044-7431(02)00013-1",
    language = "English (US)",
    volume = "22",
    pages = "285--297",
    journal = "Molecular and Cellular Neuroscience",
    issn = "1044-7431",
    publisher = "Academic Press Inc.",
    number = "3",

    }

    TY - JOUR

    T1 - Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington's disease

    AU - Senatorov, Vladimir V.

    AU - Charles, Vinod

    AU - Reddy, P (Hemachandra)

    AU - Tagle, Dan A.

    AU - Chuang, De Maw

    PY - 2003/3/1

    Y1 - 2003/3/1

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=0345701435&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0345701435&partnerID=8YFLogxK

    U2 - 10.1016/S1044-7431(02)00013-1

    DO - 10.1016/S1044-7431(02)00013-1

    M3 - Article

    C2 - 12691731

    AN - SCOPUS:0345701435

    VL - 22

    SP - 285

    EP - 297

    JO - Molecular and Cellular Neuroscience

    JF - Molecular and Cellular Neuroscience

    SN - 1044-7431

    IS - 3

    ER -