Studies have found genetic association and rare variations in the UBE3A gene that are associated with autism. Association was found in families of the Collaborative Linkage Study of Autism (Nurmi et al., 2001), and rare variants were found in cases of European ancestry.
Molecular Function
This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families.
A novel UBE3A sequence variant identified in eight related individuals with neurodevelopmental delay, results in a phenotype which does not match the clinical criteria of Angelman syndrome
Deficiency of the maternal allele of Ube3a results in impaired motor function, inducible seizures, learning deficits, abnormal hippocampal electroencephalographic recordings, and severely impaired long-term potentiation.
References
Type
Title
Author, Year
Additional
Ube3a is required for experience-dependent maturation of the neocortex.
Model Type:
Genetic
Model Genotype:
Heterozygous/ maternal deficiency
Mutation:
A targeting vector replaced a 3 kb genomic DNA fragment containing exon 2 (299 bp; bp 3302 in GenBank number U82122) deleting 100 amino acids from the N-terminal end leading to a frameshift mutation and loss of all putative protein isoforms,mice heterozygous for this allele were bred to model Angelman's syndrome with the deficiency of the maternal allele (m-).
Allele Type: Targeted (knock-out)
Strain of Origin: 129S7/SvEvBrd-Hprt1
Genetic Background: 129S7/SvEvBrd * C57BL/6
ES Cell Line: AB2.2
Mutant ES Cell Line: Not Specified
Model Source: JAX (129-Ube3atm1Alb/J)
Model Type:
Genetic
Model Genotype:
Heterozygous/ maternal deficiency
Mutation:
A targeting vector replaced a 3 kb genomic DNA fragment containing exon 2 (299 bp; bp 3302 in GenBank number U82122) deleting 100 amino acids from the N-terminal end and shifting redaing frameto inactivate all putative protein isoforms.
Allele Type: Targeted (knock-out)
Strain of Origin: 129S7/SvEvBrd-Hprt1
Genetic Background: 129S7/SvEvBrd * C57BL/6
ES Cell Line: AB2.2
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A targeting vector replaced a 3 kb genomic DNA fragment containing exon 2 (299 bp; bp 3302 in GenBank number U82122) deleting 100 amino acids from the N-terminal end and shifting redaing frameto inactivate all putative protein isoforms.
Allele Type: Targeted (knock-out)
Strain of Origin: 129S7/SvEvBrd-Hprt1
Genetic Background: 129S7/SvEvBrd
ES Cell Line: AB2.2
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Insertion of 162-kb segment of mouse chromosome 7, containing the entire 78-kb exon-intron coding sequence of Ube3a as well as its 64-kb 5' and 21-kb 3' sequence using BAC recombineering techniques.
Allele Type: Targeted (Transgenic)
Strain of Origin: FVB/NJ
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Insertion of 162-kb segment of mouse chromosome 7 ,twice, containing the entire 78-kb exon-intron coding sequence of Ube3a as well as its 64-kb 5' and 21-kb 3' sequence using BAC recombineering techniques.
Allele Type: Targeted (Transgenic)
Strain of Origin: FVB/NJ
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous/ paternal deficiency
Mutation:
A targeting vector replaced a 3 kb genomic DNA fragment containing exon 2 (299 bp; bp 3302 in GenBank number U82122) deleting 100 amino acids from the N-terminal end and shifting redaing frameto inactivate all putative protein isoforms.
Allele Type: Targeted (knock-out)
Strain of Origin: 129S7/SvEvBrd-Hprt1
Genetic Background: 129S7/SvEvBrd
ES Cell Line: AB2.2
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Conditional deletion of exon 5 of the maternal copy of the Ube3a gene using Nex-cre, in the excitatory neurons, with authors assessments aligned to neocortical glutamatergic neurons. Authors note that Nex-cre does not cause deletion of Ube3a from ventral neuron populations or majority of dentate granule neurons.
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: 27021170
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
To allow temporally controlled reactivation of the Ube3a gene, using Cre-mediated deletion, a floxed transcriptional stop cassette is inserted within intron 3 by homologous recombination. In the absence of any cre recombinase mice are devoid of Ube3a expression from the inherited STOP allele (these are Ube3a STOP/p+ mice).
Allele Type: Targeted (knockout)
Strain of Origin: Genetic Background: 129S2/SvPasCrl* C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: 27021170
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Mosaic deletion of exon 5 of Ube3a gene (maternal copy) via AAV vector containing cre recombinase were injected intracerebroventrically into neonatal pups. This produced a sparce mosaic of viral transduction in neurons, including pyramidal neurons
Allele Type: Mosaic
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: 27021170
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Ube3a STOP/p+ mice are maintained in the 129S2/SvPasCrl background for seizure experiments.
Allele Type: Targeted (knockout)
Strain of Origin: Genetic Background: 129S2/SvPasCrl
ES Cell Line: Mutant ES Cell Line: Model Source: 25866966
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Conditional deletion of exon 5 of the maternal copy of the Ube3a gene using Gad-cre, in gabaergic neurons of the neocortex (maintained on 129S2/SvPasCrl background)
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: 129S2/SvPasCrl
ES Cell Line: Mutant ES Cell Line: Model Source: 27021170
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Conditional deletion of exon 5 of the maternal copy of the Ube3a gene using Gad-cre, in gabaergic neurons of the neocortex
Allele Type: Conditional loss-of-function
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: C57BL/6
Mutant ES Cell Line: Model Source: 27021170
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Conditional deletion of exon 5 of the maternal copy of the Ube3a gene using Nestin-cre, in neuronal, glial and other cell types in the central and peripheral nervous system
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: 27021170
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Ube3a STOP/p+ mice (see UBE3A_11_KO_HE) that do not express maternally inherited Ube3a are crossed with Gad-cre heterozygous males that reinstates maternal Ube3a expression only in Gabaergic interneurons, still leaving the Cux1 positive glutamatergic interneurons devoid of maternal Ube3a. Authors use these mice to study the effects of loss of Ube3a from glutamatergic interneurons.
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: 129S2/SvPasCrl* C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: 27021170
Model Type:
Genetic
Model Genotype:
Heterozygous/ maternal deficiency
Mutation:
Same mutation as UBE3A_4_HT_p, with targeting exon 2 and loss of all isoforms of Ube3a following deletion of 100 aas from N term, the mutant allele (deficiency) in inherited maternally and the wild type allele is paternal.
Allele Type: Targeted (knockout)
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 9808466
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Ub3a overexpressing (2 fold increase in expression compared to WT) mice were generated using BAC recombineering using a 162 kb segment of Mmu17 containing the entire Ube3a exon-intron coding segment and 5' and 3' UTRs into FVB embryos. The behavioral phenotype for this model was similar whether or not the construct contains C terminal flag tags- present after exon 10 of isoform 3, therefore phenotypes of flagged and unflagged het transgenic mice expressing one additional copy of Ube3a are represented by the same model. Ube3a heterozygous transgenic mice were crossed to generate homozygous mice.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 28297715
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Ub3a overexpressing mice (1.5 fold increase in Ube3a expression) were generated using BAC recombineering using a 162 kb segment of Mmu17 containing the entire Ube3a exon-intron coding segment and 5' and 3' UTRs into FVB embryos. The behavioral phenotype for this model was similar whether or not the construct contains C terminal flag tags- present after exon 10 of isoform 3, therefore phenotypes of flagged and unflagged het transgenic mice expressing one additional copy of Ube3a are represented by the same model.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 28297715
Model Type:
Multifactorial
Model Genotype:
Homozygous
Mutation:
Transgenic mice heterozygous for BAC expressing untagged Ube3a (expression levels twice of wild type) were injected (i.p.) with subconvulsant dose of PTZ, 30mg/kg dissolved in saline, every other day, for 10 days.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 28297715
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Two in frame nuclear localization signals (NLS) were added to the C terminal, following 3 flag tags to the BAC encoding the Ube3a coding region (same as Ube3a_17_HT_TG), the mice are heterozygous for this construct and the all the Ube3a is localized to the nucleus.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 28297715
Model Type:
Multifactorial
Model Genotype:
Homozygous
Mutation:
This multifactorial model for ASD was generated using conditional overexpression of Ube3a in Slc6a3 (DAT) positive cells and induction of siezures using PTZ. Transgenic mice, homozygous for lox-TB-Ube3-flagged BAC containing a floxed transcriptional blocker in intron 1, suppressing the expression of Ube3a in the absence of cre recombinase, were crossed with Slc6a3 (DAT)-cre mice and then treated with i.p. injections of 30mg/kg (subconvulsant dosing) pentylenetetrazole (PTZ) dissolved in saline, delivered every other day for 10 days.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 28297715
Model Type:
Multifactorial
Model Genotype:
Homozygous
Mutation:
This multifactorial model for ASD was generated using conditional overexpression of Ube3a in VGLUT2 positive cells and induction of siezures using PTZ. Transgenic mice, homozygous for lox-TB-Ube3-flagged BAC containing a floxed transcriptional blocker in intron 1, suppressing the expression of Ube3a in the absence of cre recombinase, were crossed with VGLUT2-cre mice and then treated with i.p. injections of 30mg/kg (subconvulsant dosing) pentylenetetrazole (PTZ) dissolved in saline, delivered every other day for 10 days.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 28297715
Model Type:
Multifactorial
Model Genotype:
Homozygous
Mutation:
This multifactorial model for ASD was generated to study the role of overexpression of Ube3a specifically in ventral tegmental area (VTA) in combination with subconvulsant doses of pentylenetetrazole (PTZ). AAV-hSYN-DIO-UBE3A (human isoform 3) was stereotaxically injected in the VTA of Vglut2 cre mice allowing the expression of human, untagged UBE3A in the Vglut2 + cells of the VTA.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/NJ
ES Cell Line: Mutant ES Cell Line: Model Source: 28297715
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Ube3a-T503A mice were generated in C57BL/6J blastocysts using CRISPR/Cas9 insertional mutagenesis. This mouse mutation precisely models the human UBE3A-T485A mutation. The founder line was backcrossed with wildtype C57BL/6J mice for two generations prior to establishing the Ube3a-T503A colony. Backcrossing removes unlinked, random mutations that might have been introduced by CRISPR/Cas9. Heterozygous mutant mice were intercrossed to generate homozygous mutant mice (Ube3a^pT503A/mT503A).
Allele Type: ASD mutation
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: UNC Animal Model Core facility
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Ube3a-T503A mice were generated in C57BL/6J blastocysts using CRISPR/Cas9 insertional mutagenesis. This mouse mutation precisely models the human UBE3A-T485A mutation. The founder line was backcrossed with wildtype C57BL/6J mice for two generations prior to establishing the Ube3a-T503A colony. Backcrossing removes unlinked, random mutations that might have been introduced by CRISPR/Cas9. Maternal heterozygous mutant mice (Ube3a^p+/mT503A) were generated by breeding wildtype males with heterozygous or homozygous females.
Allele Type: ASD mutation
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: UNC Animal Model Core facility
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Ube3a-T503A mice were generated in C57BL/6J blastocysts using CRISPR/Cas9 insertional mutagenesis. This mouse mutation precisely models the human UBE3A-T485A mutation. The founder line was backcrossed with wildtype C57BL/6J mice for two generations prior to establishing the Ube3a-T503A colony. Backcrossing removes unlinked, random mutations that might have been introduced by CRISPR/Cas9. Paternal heterozygous mutant mice (Ube3a^pT503A/m+) and littermate control mice were generated by breeding homozygous or heterozygous mutant males with wildtype females.
Allele Type: ASD mutation
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: UNC Animal Model Core facility
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mice carrying the Ube3a knockout allele (MGI:2181811) were maintained on the C57BL/6 background in the lab. Ube3a^m-/p+(Angelman Syndrome model) and littermate control mice were generated by breeding wildtype males with Ube3a^-/+ females..
Allele Type: Knockout
Strain of Origin: 129S7/SvEvBrd-Hprt1b-m2
Genetic Background: C57BL/6J
ES Cell Line: AB2.2
Mutant ES Cell Line: Model Source: A. L. Beaudet
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A targeting vector replaced a 3 kb genomic DNA fragment containing exon 2 (299 bp; bp 3302 in GenBank number U82122) deleting 100 amino acids from the N-terminal end and shifting redaing frameto inactivate all putative protein isoforms.
Allele Type: Targeted (knock-out)
Strain of Origin: 129S7/SvEvBrd-Hprt1
Genetic Background: 129S7/SvEvBrd * C57BL/6
ES Cell Line: AB2.2
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous/ paternal deficiency
Mutation:
A targeting vector replaced a 3 kb genomic DNA fragment containing exon 2 (299 bp; bp 3302 in GenBank number U82122) deleting 100 amino acids from the N-terminal end leading to a frameshift mutation and loss of all putative protein isoforms, heterozygous mice were bred to produce paternal deficiency of Ube3a.
Allele Type: Targeted (knock-out)
Strain of Origin: 129S7/SvEvBrd-Hprt1
Genetic Background: 129S7/SvEvBrd
ES Cell Line: AB2.2
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Description: Deficit in long-term synaptic potentiation in the hippocampus
Exp Paradigm: Ltp at schaffer collateral synapses in area ca1, using high-frequency stimulation
Description: In the hippocampal slices from mice lacking maternal ube3a, if a second tbs (tbs2) applied 60 min after the first (tbs1) there is an no enhancement of ltp, unlike in wild type slices as they undergo a refractory period of about 60 min after tbs1, following which the ltp magnitude was enhanced by tbs2.
Exp Paradigm: NA
Description: In the hippocampal slices from mice lacking maternal ube3a, a second tbs applied 10 or 45 min after the first (tbs1) there is an enhancement of ltp, unlike in wild type slices as they undergo a refractory period after tbs1 during which another tbs stimulation cannot enhance ltp magnitude.
Exp Paradigm: NA
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Mice lacking maternal ube3a show significantly reduced freezing behavior compared to wild type in response to reintroduction to cs of the tone after which they received a shock previously
Exp Paradigm: NA
Cued or contextual fear conditioning: memory of context1
Decreased
Description: Mice lacking maternal ube3a show significantly reduced freezing behavior compared to wild type in response to reintroduction to cs of the context where they received a shock
Exp Paradigm: NA
Description: There is a significant reduction in the ubiquitination of sk2 (which co immunoprecipitates with ube3a and is shown separately to be ubiquitinated by ube3a in wild type), in mice lacking maternal ube3a
Exp Paradigm: NA
Description: Concominant with increased levels of sk2 the expression or localization of this protein to the puncta is also significantly increased in mice lacking maternal ube3a.
Exp Paradigm: NA
Description: Mice with maternal deficiency of ube3a have increased levels of small-conductance calcium-activated potassium channel 2 (sk2) in the synaptosomal and psd enriched subcellular fractions of the hippocampus, compared to wt controls
Exp Paradigm: NA
Description: Decreased number of dopaminergic neurons in substantia nigra
Exp Paradigm: Stereological quantification after double immunostaining with th and e6-ap antibodies in substantia nigra
Description: Deficit in long-term synaptic potentiation in the hippocampus
Exp Paradigm: Ltp at schaffer collateral synapses in area ca1, using high-frequency stimulation
Description: Abnormal synaptic transmission; absence of induction of ltd and ltp with standard stimulation and weak stimulation protocols respectively
Exp Paradigm: Whole-cell patch-clamp recordings in layer 2/3 pyramidal neurons of visual cortex after conditioning stimuli-whole-cell patch-clamp: long-term potentiation (ltp)
Description: Abnormal synaptic transmission; absence of induction of ltd and ltp with standard stimulation and weak stimulation protocols respectively
Exp Paradigm: Whole-cell patch-clamp recordings in layer 2/3 pyramidal neurons of visual cortex after conditioning stimuli- whole-cell patch-clamp: long-term depression (ltd)
Description: Decreased expression of presynaptic protein synaptophysin and postsynaptic density protein psd95 in striatum
Exp Paradigm: Synaptic protein expression
Description: Abnormal neuronal circuit morphology demonstrated by decreased density of glur1 puncta closely apposed to sv2 puncta
Exp Paradigm: Array tomography using anti-glur1 and anti-sv2 antibodies on ultra-thin sections of brain tissue
Description: Abnormal miniature inhibitory postsynaptic currents (mipsc)s indicated by decreased frequency with no change in amplitude
Exp Paradigm: Intracellular recordings in presence of erbb inhibitor pd168393 (10 micromol/l)
Neuronal activation following behavioral stimulation: arc levels1
Increased
Description: Increased expression of arc protein in response to enhanced neuronal activity
Exp Paradigm: Western blot analysis using anti-arc antibody in response to kainic acid treatment
Description: Abnormal erbb4 phosphorylation states indicated by increased levels on tyrosine 1056 and 1162 and no change on tyrosine 1188
Exp Paradigm: Erbb4 phosphorylation state
Description: Abnormal social interaction demonstrated by no preference fo social zone but significant preference to interact with cage occupied by mouse
Exp Paradigm: Three-chamber social interaction test in juveniles
Description: Decreased number of vocalizations and time spent vocalizing
Exp Paradigm: Vocalizations generated by sexually experienced males exposed to female urine
Description: Decreased epsc spike coupling with no change in actino potential threshold, capacitance, and resting membrane potential
Exp Paradigm: Patch clamp recordings after short epsc like current injections
Description: Decreased epsc amplitude in response to a weak glutamate recpetor antagonist, gamma-dgg
Exp Paradigm: Whole-cell voltage-clamp recordings in acute brain slices after administration of gamma-dgg
Description: Decreased social preference with no preference for side containing novel mouse
Exp Paradigm: Three-chamber social interaction test in adults
Description: Decreased social stimulus induced vocalizations
Exp Paradigm: Vocalizations generated by same-sex pairs encountering each other for the first time
Description: Decreased number of vocalizations and time spent vocalizing
Exp Paradigm: Vocalizations generated by sexually experienced males exposed to female urine
Description: Decreased number of pv-immunoreactive inhibitory interneurons in hippocampus
Exp Paradigm: Pv-immunohistochemical staining in dg of hippocampus
Description: Decreased gaba receptor activation demonstrated by reduced current with ambient gaba and no change with higher concentration
Exp Paradigm: NA
Description: Abnormal evoked ipsc indicated by normal paired-pulse ratio with faster decay rate
Exp Paradigm: Whole cell recordings in cerebellar granule cells
Description: Audiogenic seizure in 18% of paternal deficiency mice in inbred 129/svev background.
Exp Paradigm: Audiogenic stimulus for seizure induction
Description: Increased anxiety demonstrated by more time and distance spent in the outer zone and also increased frequency of freezing
Exp Paradigm: Open field test
Description: Abnormal gr expression demonstrated by decreased levels in hippocampus and no change in both cerebral cortex and cerebellum
Exp Paradigm: Gr protein expression-western blot
Description: Abnormal gr expression demonstrated by decreased levels in hippocampus and no change in both cerebral cortex and cerebellum
Exp Paradigm: Gr protein expression- immunohistochemistry: fluorescence
Description: Decreased level of expression of sgk1 in cerebral cortex, hippocampus and cerebellum
Exp Paradigm: Sgk1 protein expression- immunohistochemistry: fluorescence
Description: Tonic currents mediated by extrasynaptic delta subunit containing gabaa receptors (also sensitive to thip/gabazine) are decreased in mice lacking maternal ube3a from neocortical glutamatergic interneurons, authors note that these are the main mediators of tonic inhibition onto pyramidal neurons of layer 2-3 and this effect is cell-autonomous for glutamatergic cells lacking ube3a
Exp Paradigm: NA
Miniature post synaptic current amplitude: inhibitory1
Decreased
Description: Evoked miniature ipscs have decreased amplitude in the layer 2-3 pyramidal neurons of the visual cortex in cko mice lacking maternal ube3a in most neocortical glutamatergic interneurons,
Exp Paradigm: NA
Description: There is increased accumulation of clathrin-coated vesicles in the presynaptic terminals of mice lacking maternal ube3a from all neurons (ube3a stop/+), indicating reduced recycling mediated by the clathrin coated endocytic pathway
Exp Paradigm: NA
Miniature post synaptic current amplitude: inhibitory1
Decreased
Description: Evoked ipscs have reduced amplitude in pyramidal neurons (l2-3) lacking ube3a (and positive for tdtomato) in mice injected with adeno-associated virus containing cre
Exp Paradigm: NA
Description: Total spectral power is increased in mice lacking maternal ube3a from all neurons (ube3a stop/p+)measured by recording resting state local field potential or intracortical eeg
Exp Paradigm: NA
Description: Ube3a stop/p+ mice are much more susceptible to audiogenic seizures in frequency and latency compared to control littermates
Exp Paradigm: NA
Description: Total spectral power is increased (authors note a trend) in mice lacking maternal ube3a from gabaergic neurons in 129s2/svpascrl background
Exp Paradigm: NA
Description: Spontaneous seizures are significantly increased in mice lacking maternal ube3a from gabaergic neurons in 129s2/svpascrl background
Exp Paradigm: NA
Description: Mice lacking maternal ube3a from gabaergic neurons in 129s2/svpascrl background exhibit audiogenic seizures much more frequently than control littermates with an increased chance of progressing from wild running to tonic-clonic seizures
Exp Paradigm: NA
Description: Total spectral power is increased in cko mice lacking maternal ube3a gabaergic neurons measured by recording resting state local field potential or intracortical eeg
Exp Paradigm: Electroencephalogram (eeg)
Description: There is increased accumulation of clathrin-coated vesicles in the presynaptic terminals of gabaergic interneurons in cko mice lacking maternal ube3a from gabaergic interneurons indicating deficient recycling of synaptic vesicles from the clathrin dependent endocytic pathway
Exp Paradigm: NA
Description: A significant decrease in the latency to myoclonic and generalized seizures induced by flurothyl is observed in mice lacking maternal ube3a from gabaergic interneurons
Exp Paradigm: NA
Description: Ube3a is selectively lost in almost all gabaaergic interneurons in the primary visual cortex, sparing layer 2-4 cux1 positive cells
Exp Paradigm: NA
Description: There is increased accumulation of clathrin-coated vesicles in the presynaptic terminals of gabaergic interneurons in cko mice lacking ube3a in the nervous system indicating deficient recycling of synaptic vesicles from the clathrin dependent endocytic pathway
Exp Paradigm: NA
Miniature post synaptic current amplitude: inhibitory1
Decreased
Description: Evoked miniature ipscs have decreased amplitude in the layer 2-3 pyramidal neurons of the visual cortex in cko mice lacking maternal ube3a in the nervous system
Exp Paradigm: Whole-cell patch clamp: layer 2-3 pyramidal neurons of visual cortex
Spontaneous post synaptic event frequency: inhibitory currents1
Decreased
Description: Spontaneous miniature ipscs have decreased frequency in layer 2-3 pyramidal neurons of the visual cortex in cko mice lacking maternal ube3a in the nervous system
Exp Paradigm: NA
Spontaneous post synaptic event amplitude: inhibitory currents1
Decreased
Description: Spontaneous miniature ipscs have decreased amplitude in layer 2-3 pyramidal neurons of the visual cortex in cko mice lacking maternal ube3a in the nervous system
Exp Paradigm: NA
Miniature post synaptic current amplitude: inhibitory1
Decreased
Description: Evoked miniature ipscs have decreased amplitude in the layer 2-3 pyramidal neurons of the visual cortex in cko mice lacking maternal ube3a in most glutamatergic, cux1 positive interneurons and all other neurons except gabaergic interneurons where they are reinstated, authors note that the difference is not statistically significant but still draw some conclusions on the role of glutamatergic neurons vs gabaergic neurons in these mice
Exp Paradigm: Whole-cell patch clamp: layer 2-3 pyramidal neurons of visual cortex
Description: Ube3a 2x mice have decreased time in contact during the reciprocal interaction test where they were also tested for vocalizations
Exp Paradigm: NA
Description: Mutant mice, designated as ube3a 2x homozygous for ube3a transgene express times the level of ube3a expressed by wild type mice
Exp Paradigm: NA
Description: Ube3a 1x (expressing increased ube3a) mice treated with 5 injections of ptz display impaired social approach, 24 hrs after last treatment
Exp Paradigm: NA
Description: Ube3a nls mice spend less time in contact with the paired mouse during reciprocal interaction test, during which the vocalizations were also tested
Exp Paradigm: NA
Description: Ube3a nls mice have impaired social approach in the three chamber social approach test and spend less time with stimulus mouse than the empty chamber
Exp Paradigm: NA
Description: Ube3a nls mice display increased anxiety and spend a significantly less amount of time in the open arms of the elevated plus maze compared to wt
Exp Paradigm: NA
Description: Impaired social approach is observed after combination of increased expression of ube3a selectively in slc6a3 (dopamine transporter) positive neurons and induction of seizures in mice, indicating the role of ube3a in slc6a3 positive cells in causing increased susceptibility to social impairment
Exp Paradigm: NA
Description: Impaired social approach is observed after combination of increased expression of ube3a selectively in vglut2 positive neurons and induction of seizures in mice, indicating the role of ube3a in vglut2 positive cells in causing increased susceptibility to social impairment
Exp Paradigm: NA
Description: Increased expression of ube3a (human isoform 3) via expression from a viral vector stereotaxically injected into the ventral tegmental area (vta) in addition to ptz treatment impaired social approach in mice (whereas increasing ube3a expression in vta only did not lead to this impairment)
Exp Paradigm: NA
Description: Homozygous knockin shows protein levels for PSMD1, PSMD4, NEURL4 are decreased while protein levels for PSMB1, PSMA2, PSMD2, ERK3 are unchanged
Description: Heterozygous maternal knockin shows reduced expression in the ventricular and subventricular zones, in cortical neurons and oligodendrocytes.
Description: Heterozygous paternal knockin shows reduced expression in the ventricular and subventricular zones and oligodendrocytes, but not reduced in cortical neurons.
