altered ultrasonic vocalization and impaired learning and memory in angelman syndrome mouse model with a large maternal deletion from ube3a to gabrb3改变超声波发声与学习和记忆受损angelman综合征小鼠模型,孕产妇删除从ube3a gabrb3.pdfVIP

Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3 1,2 1 2 1 3 1 1 Yong-hui Jiang *, Yanzhen Pan , Li Zhu , Luis Landa , Jong Yoo , Corinne Spencer , Isabel Lorenzo , 4¤ 3 1 Murray Brilliant , Jeffrey Noebels , Arthur L. Beaudet 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America, 2 Division of Medical Genetics, Department of Pediatrics and Neurobiology, Duke University School of Medicine, Durham, North Carolina, United States of America, 3 Neurogenetics Laboratory of Department of Neurology, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Pediatrics, University of Arizona Health Science Center, Tucson, Arizona, United States of America Abstract Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11–q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11–q13. Using a chromosomal engineering strategy, we generated mutant mi