DOI: 10.1073/pnas.110078997. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

10.1073/pnas.110078997

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Huntington's disease (HD) is a fatal inherited neurodegenerative disorder characterized by personality changes, motor impairment, and subcortical dementia. HD is one of a number of diseases caused by expression of an expanded polyglutamine repeat. We have developed several lines of mice that are transgenic for exon 1 of the HD gene containing an expanded CAG sequence. These mice exhibit a defined neurological phenotype along with neuronal changes that are pathognomonic for the disease. We have previously observed the appearance of neuronal intranuclear inclusions, but did not find evidence for neurodegeneration. In this study, we report that all lines of these mice develop a late onset neurodegeneration within the anterior cingulate cortex, dorsal striatum, and of the Purkinje neurons of the cerebellum. Dying neurons characteristically exhibit neuronal intranuclear inclusions, condensation of both the cytoplasm and nucleus, and ruffling of the plasma membrane while maintaining ultrastructural preservation of cellular organelles. These cells do not develop blebbing of the nucleus or cytoplasm, apoptotic bodies, or fragmentation of DNA. Neuronal death occurs over a period of weeks not hours. We also find degenerating cells of similar appearance within these same regions in brains of patients who had died with HD. We therefore suggest that the mechanism of neuronal cell death in both HD and a transgenic mouse model of HD is neither by apoptosis nor by necrosis.

Bibliography

Turmaine, M., Raza, A., Mahal, A., Mangiarini, L., Bates, G. P., & Davies, S. W. (2000). Nonapoptotic neurodegeneration in a transgenic mouse model of Huntingtonâs disease. Proceedings of the National Academy of Sciences, 97(14), 8093â8097.

Authors 6

Mark Turmaine (first)
Aysha Raza (additional)
Amarbirpal Mahal (additional)
Laura Mangiarini (additional)
Gillian P. Bates (additional)
Stephen W. Davies (additional)

References 33 Referenced 347

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10.1111/j.1750-3639.1997.tb00893.x
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10.1016/S0092-8674(00)81369-0
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10.1098/rstb.1999.0448
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10.1073/pnas.96.8.4604
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M Dragunow, R L M Faull, P Lawlor, E J Beihartz, K Singleton, E B Walker, E Mee Clin Neurosci Neuropathol 6, 1053–1057 (1995). / Clin Neurosci Neuropathol by Dragunow M (1995)
10.1006/exnr.1995.1029
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10.1111/j.1365-2990.1995.tb01024.x

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:37 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:20 p.m.)
Indexed	2 weeks, 1 day ago (Aug. 20, 2025, 8:32 a.m.)
Issued	25 years, 2 months ago (June 27, 2000)
Published	25 years, 2 months ago (June 27, 2000)
Published Online	25 years, 2 months ago (June 27, 2000)
Published Print	25 years, 1 month ago (July 5, 2000)

Funders 0

None

BibTeX

@article{Turmaine_2000, title={Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington’s disease}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.110078997}, DOI={10.1073/pnas.110078997}, number={14}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Turmaine, Mark and Raza, Aysha and Mahal, Amarbirpal and Mangiarini, Laura and Bates, Gillian P. and Davies, Stephen W.}, year={2000}, month=jun, pages={8093–8097} }

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