title: Expression of Huntington's disease protein results in apoptotic neurons in the brains of cloned transgenic pigs.
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.
authors.affiliation: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Dongshan
authors.initials: D
authors.lastname: Yang
authors.forename: Chuan-En
authors.initials: CE
authors.lastname: Wang
authors.forename: Bentian
authors.initials: B
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Liu
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Yang
authors.forename: Pei
authors.initials: P
authors.lastname: Fan
authors.forename: Ashley
authors.initials: A
authors.lastname: O'Neill
authors.forename: Weiwang
authors.initials: W
authors.lastname: Gu
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Shihua
authors.initials: S
authors.lastname: Li
authors.forename: Liangxue
authors.initials: L
authors.lastname: Lai
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000096:biosynthesis; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D015870:Gene Expression; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D019636:Neurodegenerative Diseases; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D057165:Proteostasis Deficiencies; D013045:Species Specificity; D013552:Swine / Q000235:genetics / Q000378:metabolism; D013556:Swine, Miniature / Q000235:genetics / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D053148:Caspase 3