adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for angelman syndrome腺相关virus-mediated救援认知缺陷的小鼠模型angelman综合征.pdfVIP

Adeno-Associated Virus-Mediated Rescue of the Cognitive Defects in a Mouse Model for Angelman Syndrome Jennifer L. Daily1,4, Kevin Nash1,4, Umesh Jinwal2,4, Todd Golde5,6, Justin Rogers1,4, Melinda M. Peters1,4, Rebecca D. Burdine3, Chad Dickey4,7, Jessica L. Banko4,7, Edwin J. Weeber1,4* 1 Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, United States of America, 2 Department of Pharmacy, University of South Florida, Tampa, Florida, United States of America, 3 Department of Neuroscience, Princeton University, Princeton, New Jersey, United States of America, 4 University of South Florida Health Byrd Alzheimer’s Institute, Tampa, Florida, United States of America, 5 McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America, 6 Center for Translational Research in Neurodegenerative Diseases, University of Florida, Gainesville, Florida, United States of America, 7 Department of Molecular Medicine, University of South Florida, Tampa, Florida, United States of America Abstract Angelman syndrome (AS), a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. However, we have determined that abnormal calcium/calmodu