1998
DOI: 10.1016/s0896-6273(00)80596-6
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Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation

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 … Show more

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Cited by 780 publications
(984 citation statements)
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“…Some findings suggest that the 129 strain confers greater susceptibility to gene disruption, 61,65 but, in the case of Ube3A-null mice, also leads to higher rates of seizures and mortality. 89 The 129S1/SvImJ strain demonstrates low social approach in our three-chambered choice task, 17 which could confound the detection of social deficits in mutant mice with this background.…”
Section: Discussionmentioning
confidence: 99%
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“…Some findings suggest that the 129 strain confers greater susceptibility to gene disruption, 61,65 but, in the case of Ube3A-null mice, also leads to higher rates of seizures and mortality. 89 The 129S1/SvImJ strain demonstrates low social approach in our three-chambered choice task, 17 which could confound the detection of social deficits in mutant mice with this background.…”
Section: Discussionmentioning
confidence: 99%
“…Reduced expression of UBE3A in cerebral tissue has been reported for autism and Rett syndrome, as well as AS, albeit in a small number of samples. 87 Mice with maternal deficiency of Ube3a (mÀ/p þ ) have deficits in motor coordination and context-dependent fear conditioning, [88][89][90] reduced spatial learning in the Morris water maze task, 88,90 and enhanced seizure susceptibility. 88,89 More severe symptoms in AS may involve the contribution of other genes in the 15q11-13 region, including GABRB3, which encodes the b3-subunit of the g-aminobutyric acid (GABA) type A receptor.…”
Section: Mouse Models Of Genetic Clinical Disorders With Autism Symptmentioning
confidence: 99%
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“…Mouse models generated by targeted inactivation of Ube3a provide additional support to the causative role of UBE3A mutations in AS [35,36]. Upon inheritance of Ube3a deletion through the maternal but not the paternal germline, mice recapitulate many features of the human disorder, displaying impaired motor function, seizures, and deficits in contextdependent and spatial learning (summarized in Table 2 and discussed below).…”
Section: As Mouse Modelsmentioning
confidence: 99%
“…However, these animals gradually develop behavioral defects and neuronal cell death (Goldberg, Fleming, Palacino, Cepeda, & Lam, 2003). In addition, the ubiquitin ligase UBE3A (ubiquitin protein ligase E3A) destabilizes p53, the heterozygous ablation of which causes significant memory loss and dementia phenotypes among genetically engineered mice (Jiang, Armstrong, Albrecht, Atkins, & Noebels, 1998). CHIP, a tau protein E3 ligase, functions to clear phosphorylated tau in neurons, and deletion of CHIP correspondingly results in the accumulation of hyperphosphorylated tau protein and facilitates the progression of AD (Dickey, Yue, Lin, Dickson, & Dunmore, 2006).…”
Section: Pathological Contributions Of the Ubiquitin–proteasome Systementioning
confidence: 99%