Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes
نویسندگان
چکیده
منابع مشابه
The spectrum of mutations in UBE3A causing Angelman syndrome.
Angelman syndrome (AS) is characterized by mental retardation, absence of speech, seizures and motor dysfunction. AS is caused by maternal deletions for chromosome 15q11-q13, paternal uniparental disomy (UPD), imprinting defects or loss-of-function mutations in the UBE3A locus which encodes E6-AP ubiquitin-protein ligase. The UBE3A gene is imprinted with paternal silencing in human brain and si...
متن کاملGABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility
Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, ...
متن کاملMaternal UBE3A in Angelman syndrome: "the rest is silence"?
Many a parent of a child with a neurogenetic condition (surprisingly) little pathological material has been available often wonders whether ’tis nobler in the mind to suffer the slings and arrows of outrageous fortune or to contemplate hope for effective treatment. With regard to Angelman syndrome, recent results from molecular biology have opened unsuspected avenues for circumventing the molec...
متن کاملPersistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice
Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paterna...
متن کاملUbe3a Imprinting Impairs Circadian Robustness in Angelman Syndrome Models
BACKGROUND The paternal allele of Ube3a is silenced by imprinting in neurons, and Angelman syndrome (AS) is a disorder arising from a deletion or mutation of the maternal Ube3a allele, which thereby eliminates Ube3a neuronal expression. Sleep disorders such as short sleep duration and increased sleep onset latency are very common in AS. RESULTS We found a unique link between neuronal imprinti...
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ژورنال
عنوان ژورنال: Molecular Autism
سال: 2019
ISSN: 2040-2392
DOI: 10.1186/s13229-019-0277-1