Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation

Yong hui Jiang, Dawna Armstrong, Urs Albrecht, Coleen M Atkins, Jeffrey L. Noebels, Gregor Eichele, J. David Sweatt, Arthur L. Beaudet

Research output: Contribution to journalArticle

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Abstract

The E6-AP ubiquitin ligase (human/mouse gene UBE3A/Ube3a) promotes the degradation of p53 in association with papilloma E6 protein, and maternal deficiency causes human Angelman syndrome (AS). Ube3a is imprinted with silencing of the paternal allele in hippocampus and cerebellum in mice. We found that the phenotype of mice with maternal deficiency (m-/p+) for Ube3a resembles human AS with motor dysfunction, inducible seizures, and a Context- dependent learning deficit. Long-term potentiation (LTP) was severely impaired in m-/p+ mice despite normal baseline synaptic transmission and neuroanatomy, indicating that ubiquitination may play a role in mammalian LTP and that LTP may be abnormal in AS. The cytoplasmic abundance of p53 was increased in postmitotic neurons in m-/p+ mice and in AS, providing a potential biochemical basis for the phenotype through failure to ubiquitinate and degrade various effectors.

Original languageEnglish
Pages (from-to)799-811
Number of pages13
JournalNeuron
Volume21
Issue number4
DOIs
StatePublished - Oct 1 1998
Externally publishedYes

Fingerprint

Angelman Syndrome
Long-Term Potentiation
Ligases
Ubiquitin
Learning
Mutation
Mothers
Phenotype
Neuroanatomy
Protein Deficiency
Ubiquitination
Papilloma
Synaptic Transmission
Cerebellum
Hippocampus
Seizures
Alleles
Neurons
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. / Jiang, Yong hui; Armstrong, Dawna; Albrecht, Urs; Atkins, Coleen M; Noebels, Jeffrey L.; Eichele, Gregor; Sweatt, J. David; Beaudet, Arthur L.

In: Neuron, Vol. 21, No. 4, 01.10.1998, p. 799-811.

Research output: Contribution to journalArticle

Jiang, Yong hui ; Armstrong, Dawna ; Albrecht, Urs ; Atkins, Coleen M ; Noebels, Jeffrey L. ; Eichele, Gregor ; Sweatt, J. David ; Beaudet, Arthur L. / Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. In: Neuron. 1998 ; Vol. 21, No. 4. pp. 799-811.
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