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Author Notes:

To whom correspondence should be addressed. Email: lai_liangxue@gibh.ac.cn (L.L.) and xli2@emory.edu (X.-J.L.).

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Research Funding:

This work was supported by grants AG019206 and NS041669 (X.J.L.) and NS045016 and AG031153 (S.H.L.) from the National Institutes of Health, and grants from the National High Technology Research and Development Program of China (2006AA02A103), the National 973 Program of China (2009CB941001) and Natural Science Foundation of Guangdong Province, China (9251066302000001, 8451066302001811) to L.X.L.

Expression of Huntington's disease protein results in apoptotic neurons in the brains of cloned transgenic pigs

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Journal Title:

Human Molecular Genetics

Volume:

Volume 19, Number 20

Publisher:

, Pages 3983-3994

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Neurodegeneration is a hallmark of many neurological diseases, including Alzheimer's, Parkinson's and the polyglutamine diseases, which are all caused by misfolded proteins that accumulate in neuronal cells of the brain. Although apoptosis is believed to contribute to neurodegeneration in these cases, genetic mouse models of these diseases often fail to replicate apoptosis and overt neurodegeneration in the brain. Using nuclear transfer, we generated transgenic Huntington's disease (HD) pigs that express N-terminal (208 amino acids) mutant huntingtin with an expanded polyglutamine tract (105Q). Postnatal death, dyskinesia and chorea-like movement were observed in some transgenic pigs that express mutant huntingtin. Importantly, the transgenic HD pigs, unlike mice expressing the same transgene, displayed typical apoptotic neurons with DNA fragmentation in their brains. Also, expression of mutant huntingtin resulted in more neurons with activated caspase-3 in transgenic pig brains than that in transgenic mouse brains. Our findings suggest that species differences determine neuropathology and underscore the importance of large mammalian animals for modeling neurological disorders.

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© The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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