Show simple item record Jiang, YH Pan, Y Zhu, L Landa, L Yoo, J Spencer, C Lorenzo, I Brilliant, M Noebels, J Beaudet, AL
dc.coverage.spatial United States 2011-06-21T17:32:12Z 2010-08-20
dc.identifier.citation PLoS One, 2010, 5 (8), pp. e12278 - ?
dc.description.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 mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.
dc.format.extent e12278 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0012278
dc.subject Adenosine Triphosphatases
dc.subject Angelman Syndrome
dc.subject Animals
dc.subject Cerebral Cortex
dc.subject Chromosome Deletion
dc.subject Darkness
dc.subject Disease Models, Animal
dc.subject Exploratory Behavior
dc.subject Female
dc.subject Gene Expression Regulation
dc.subject Homozygote
dc.subject Male
dc.subject Membrane Transport Proteins
dc.subject Memory
dc.subject Mice
dc.subject Mothers
dc.subject Motor Activity
dc.subject Receptors, GABA-A
dc.subject Seizures
dc.subject Ubiquitin-Protein Ligases
dc.subject Ultrasonics
dc.subject Vocalization, Animal
dc.title Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-8-20 en_US
duke.description.endpage e12278 en_US
duke.description.issue 8 en_US
duke.description.startpage e12278 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US
pubs.issue 8
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Neurobiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics/Pediatrics, Medical Genetics
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1932-6203

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