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

Published

Journal Article

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.

Full Text

Cited Authors

  • Jiang, YH; Armstrong, D; Albrecht, U; Atkins, CM; Noebels, JL; Eichele, G; Sweatt, JD; Beaudet, AL

Published Date

  • October 1998

Published In

Volume / Issue

  • 21 / 4

Start / End Page

  • 799 - 811

PubMed ID

  • 9808466

Pubmed Central ID

  • 9808466

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/s0896-6273(00)80596-6

Language

  • eng