【摘 要】
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Neurodegeneration is a hallmark of many neurological diseases, including Alzheimers, Parkinsons and the polyglutamine diseases, which are all caused by misfolded proteins that accumulate in neuronal c
【机 构】
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Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative
【出 处】
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2011东莞第二届国际小型猪学术论坛暨大型实验动物生物医药研究应用研讨会
论文部分内容阅读
Neurodegeneration is a hallmark of many neurological diseases, including Alzheimers, Parkinsons 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 Huntingtons disease (HD) pigs that express N-terminal (208amino 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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