Human Molecular Genetics, Vol 5, 1093-1099, Copyright © 1996 by Oxford University Press
KE De Rooij, JC Dorsman, MA Smoor, JT Den Dunnen and GJ Van Ommen
Huntington's disease is a progressive neurodegenerative disorder, which is
caused by expansion of a polymorphic (CAG)n repeat in the coding region of
the Huntington's disease gene. The function of huntingtin has not been
elucidated so far. Accordingly, detailed subcellular localization studies
remain useful. In an immunohistochemical study, we have reported huntingtin
to be present in the cytoplasm of cells in the majority of the tissues
studied. In addition, we detected a signal in the nucleus of cells in some
tissues, including neuronal cells. We have further extended these studies
in various mammalian cell lines, using a panel of (affinity-purified)
polyclonal huntingtin antibodies in immunofluorescence, confocal laser
scanning microscopy and biochemical subcellular fractionation studies. In
mouse embryonic fibroblasts, human skin fibroblasts and in mouse
neuroblastoma cells huntingtin was present in the cytoplasm. All five
antibodies, directed against different parts of huntingtin, also showed a
signal in the nucleus. This signal could be competed by the original
antigen. The localization of huntingtin in both cytoplasm and nucleus, was
confirmed by biochemical subcellular fractionation studies. However, in
most other studies, a nuclear location for huntingtin has not been found.
Our results suggest, however, that besides its function(s) in the
cytoplasm, a nuclear function of huntingtin at some stages of
differentiation or in some phases of the cell cycle may not be excluded.
ARTICLES
Subcellular localization of the Huntington's disease gene product in cell lines by immunofluorescence and biochemical subcellular fractionation
MGC-Department of Human Genetics, Leiden University, The Netherlands.
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