Linked Life Data

20808828

Source:http://linkedlifedata.com/resource/pubmed/id/20808828

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-9-2
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1932-6203
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e12278
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20808828-Adenosine Triphosphatases, pubmed-meshheading:20808828-Angelman Syndrome, pubmed-meshheading:20808828-Animals, pubmed-meshheading:20808828-Cerebral Cortex, pubmed-meshheading:20808828-Chromosome Deletion, pubmed-meshheading:20808828-Darkness, pubmed-meshheading:20808828-Disease Models, Animal, pubmed-meshheading:20808828-Exploratory Behavior, pubmed-meshheading:20808828-Female, pubmed-meshheading:20808828-Gene Expression Regulation, pubmed-meshheading:20808828-Homozygote, pubmed-meshheading:20808828-Male, pubmed-meshheading:20808828-Membrane Transport Proteins, pubmed-meshheading:20808828-Memory, pubmed-meshheading:20808828-Mice, pubmed-meshheading:20808828-Mothers, pubmed-meshheading:20808828-Motor Activity, pubmed-meshheading:20808828-Receptors, GABA-A, pubmed-meshheading:20808828-Seizures, pubmed-meshheading:20808828-Ubiquitin-Protein Ligases, pubmed-meshheading:20808828-Ultrasonics, pubmed-meshheading:20808828-Vocalization, Animal
pubmed:year
2010
pubmed:articleTitle
Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.
pubmed:affiliation
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America. yong-hui.jiang@duke.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural