Expression of Mutated Huntingtin Fragment in the Putamen Is Sufficient to Produce Abnormal.docVIP

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Expression of Mutated Huntingtin Fragment in the Putamen Is Sufficient to Produce Abnormal.doc

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Expression of Mutated Huntingtin Fragment in the Putamen Is Sufficient to Produce Abnormal

Expression of Mutated Huntingtin Fragment in the Putamen Is Sufficient to Produce Abnormal Movement in Non-human Primates Stéphane?Palfi1,2, Emmanuel?Brouillet1, Béchir?Jarraya1,2, Jocelyne?Bloch3, Caroline?Jan1, Masahiro?Shin1, Fran?oise?Condé1, Xiao-Jiang?Li4, Patrick?Aebischer5, Philippe?Hantraye1 and Nicole?Déglon1 1Atomic Energy Commission (CEA), Institute of Biomedical Imaging, MIRCen, Place du Général Leclerc, Orsay, France 2Neurosurgery Department, Henri Mondor Hospital, AP-HP, Paris 12 University, Créteil, France 3Division of Neurosurgery, Lausanne University Medical School, Lausanne, Switzerland 4Department of Human Genetics, Emory University, Atlanta, Georgia, USA 5Ecole Polytechnique Fédérale de Lausanne (EPFL), Brain Mind Institute, Lausanne, Switzerland Correspondence: Nicole Déglon, Atomic Energy Commission (CEA), Institute of Biomedical Imaging, MIRCen, CEA/CNRS URA2210 Unit, 4, Place du Général Leclerc, 91401 Orsay, France. E-mail: nicole.deglon@cea.fr Received 14?December?2006; Accepted 2?April?2007; Published online 1?May?2007. Top of page Abstract Huntingtons disease (HD) is a neurological disorder characterized by striatal degeneration, motor symptoms and complex neuropsychiatric alterations. There is currently no genetic model of HD in non-human primates (NHPs). In this study we investigated neuropathological and behavioral changes following injections of lentiviral vectors encoding a fragment of mutated huntingtin (Htt171-82Q) into the dorsolateral sensorimotor putamen of macaques. In the first study, we injected Htt171-82Q into one hemisphere and a lentiviral vector encoding Htt171-19Q or saline into the other, and studied the animals for 9 weeks. During this period, when apomorphine was administered into Htt171-19Q/82Q animals, it induced progressive chorea, dystonia and ipsilateral turning behavior, whereas animals infected with Htt171-19Q/19Q showed no abnormal behavior. After 9 weeks, the putamen of animals infected with Htt171-82Q