Journal Article

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

Dongshan Yang, Chuan-En Wang, Bentian Zhao, Wei Li, Zhen Ouyang, Zhaoming Liu, Huaqiang Yang, Pei Fan, Ashley O'Neill, Weiwang Gu, Hong Yi, Shihua Li, Liangxue Lai and Xiao-Jiang Li

in Human Molecular Genetics

Volume 19, issue 20, pages 3983-3994
Published in print October 2010 | ISSN: 0964-6906
Published online July 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq313
Expression of Huntington's disease protein results in apoptotic neurons in the brains of cloned transgenic pigs

Show Summary Details

Preview

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.

Journal Article.  6610 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.