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Article ; Online: A Novel Automated Approach for Improving Standardization of the Marble Burying Test Enables Quantification of Burying Bouts and Activity Characteristics.

Wahl, Lucas / Punt, A Mattijs / Arbab, Tara / Willuhn, Ingo / Elgersma, Ype / Badura, Aleksandra

2022 Volume 9, Issue 2

Abstract: The marble burying test is a commonly used paradigm to describe phenotypes in mouse models of neurodevelopmental and psychiatric disorders. The current methodological approach relies predominantly on reporting the number of buried marbles at the end of ... ...

Abstract	The marble burying test is a commonly used paradigm to describe phenotypes in mouse models of neurodevelopmental and psychiatric disorders. The current methodological approach relies predominantly on reporting the number of buried marbles at the end of the test. By measuring the proxy of the behavior (buried marbles), many important characteristics regarding the temporal aspect of this assay are lost. Here, we introduce a novel, automated method to quantify mouse behavior during the marble burying test with the focus on the burying bouts and movement dynamics. Using open-source software packages, we trained a supervised machine learning algorithm (the "classifier") to distinguish burying behavior in freely moving mice. In order to confirm the classifier's accuracy and characterize burying events in high detail, we performed the marble burying test in three mouse models:
MeSH term(s)	Animals ; Behavior, Animal ; Calcium Carbonate ; Disease Models, Animal ; Humans ; Mice ; Nerve Tissue Proteins ; Obsessive-Compulsive Disorder ; Reference Standards
Chemical Substances	Nerve Tissue Proteins ; Sapap3 protein, mouse ; Shank2 protein, mouse ; Calcium Carbonate (H0G9379FGK)
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0446-21.2022
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Article ; Online: A cross-species spatiotemporal proteomic analysis identifies UBE3A-dependent signaling pathways and targets.

Pandya, Nikhil J / Meier, Sonja / Tyanova, Stefka / Terrigno, Marco / Wang, Congwei / Punt, A Mattijs / Mientjes, E J / Vautheny, Audrey / Distel, Ben / Kremer, Thomas / Elgersma, Ype / Jagasia, Ravi

Molecular psychiatry

2022 Volume 27, Issue 5, Page(s) 2590–2601

Abstract: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A. Restoring UBE3A levels is a potential disease-modifying therapy for AS and has recently entered clinical trials. There is paucity of data ... ...

Abstract	Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A. Restoring UBE3A levels is a potential disease-modifying therapy for AS and has recently entered clinical trials. There is paucity of data regarding the molecular changes downstream of UBE3A hampering elucidation of disease therapeutics and biomarkers. Notably, UBE3A plays an important role in the nucleus but its targets have yet to be elucidated. Using proteomics, we assessed changes during postnatal cortical development in an AS mouse model. Pathway analysis revealed dysregulation of proteasomal and tRNA synthetase pathways at all postnatal brain developmental stages, while synaptic proteins were altered in adults. We confirmed pathway alterations in an adult AS rat model across multiple brain regions and highlighted region-specific differences. UBE3A reinstatement in AS model mice resulted in near complete and partial rescue of the proteome alterations in adolescence and adults, respectively, supporting the notion that restoration of UBE3A expression provides a promising therapeutic option. We show that the nuclear enriched transketolase (TKT), one of the most abundantly altered proteins, is a novel direct UBE3A substrate and is elevated in the neuronal nucleus of rat brains and human iPSC-derived neurons. Taken together, our study provides a comprehensive map of UBE3A-driven proteome remodeling in AS across development and species, and corroborates an early UBE3A reinstatement as a viable therapeutic option. To support future disease and biomarker research, we present an accessible large-scale multi-species proteomic resource for the AS community ( https://www.angelman-proteome-project.org/ ).
MeSH term(s)	Angelman Syndrome/drug therapy ; Angelman Syndrome/genetics ; Angelman Syndrome/metabolism ; Animals ; Disease Models, Animal ; Mice ; Proteome ; Proteomics ; Rats ; Signal Transduction ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	Proteome ; Ube3a protein, mouse (EC 2.3.2.26) ; Ube3a protein, rat (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2022-03-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-022-01484-z
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Article ; Online: Molecular and behavioral consequences of Ube3a gene overdosage in mice.

Punt, A Mattijs / Judson, Matthew C / Sidorov, Michael S / Williams, Brittany N / Johnson, Naomi S / Belder, Sabine / den Hertog, Dion / Davis, Courtney R / Feygin, Maximillian S / Lang, Patrick F / Jolfaei, Mehrnoush Aghadavoud / Curran, Patrick J / van IJcken, Wilfred Fj / Elgersma, Ype / Philpot, Benjamin D

JCI insight

2022 Volume 7, Issue 18

Abstract: Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a severe neurodevelopmental disorder characterized by intellectual disability, impaired motor coordination, and autism spectrum disorder. Chromosomal multiplication of the UBE3A gene is ... ...

Abstract	Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a severe neurodevelopmental disorder characterized by intellectual disability, impaired motor coordination, and autism spectrum disorder. Chromosomal multiplication of the UBE3A gene is presumed to be the primary driver of Dup15q pathophysiology, given that UBE3A exhibits maternal monoallelic expression in neurons and that maternal duplications typically yield far more severe neurodevelopmental outcomes than paternal duplications. However, studies into the pathogenic effects of UBE3A overexpression in mice have yielded conflicting results. Here, we investigated the neurodevelopmental impact of Ube3a gene overdosage using bacterial artificial chromosome-based transgenic mouse models (Ube3aOE) that recapitulate the increases in Ube3a copy number most often observed in Dup15q. In contrast to previously published Ube3a overexpression models, Ube3aOE mice were indistinguishable from wild-type controls on a number of molecular and behavioral measures, despite suffering increased mortality when challenged with seizures, a phenotype reminiscent of sudden unexpected death in epilepsy. Collectively, our data support a model wherein pathogenic synergy between UBE3A and other overexpressed 15q11.2-q13.1 genes is required for full penetrance of Dup15q syndrome phenotypes.
MeSH term(s)	Animals ; Autism Spectrum Disorder ; Chromosome Aberrations ; Chromosomes, Human, Pair 15 ; Humans ; Intellectual Disability/genetics ; Intellectual Disability/pathology ; Mice ; Mice, Transgenic ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	Ube3a protein, mouse (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2022-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.158953
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Article ; Online: Dual-isoform hUBE3A gene transfer improves behavioral and seizure outcomes in Angelman syndrome model mice.

Judson, Matthew C / Shyng, Charles / Simon, Jeremy M / Davis, Courtney R / Punt, A Mattijs / Salmon, Mirabel T / Miller, Noah W / Ritola, Kimberly D / Elgersma, Ype / Amaral, David G / Gray, Steven J / Philpot, Benjamin D

JCI insight

2021 Volume 6, Issue 20

Abstract: Loss of the maternal UBE3A allele causes Angelman syndrome (AS), a debilitating neurodevelopmental disorder. Here, we devised an AS treatment strategy based on reinstating dual-isoform expression of human UBE3A (hUBE3A) in the developing brain. Kozak ... ...

Abstract	Loss of the maternal UBE3A allele causes Angelman syndrome (AS), a debilitating neurodevelopmental disorder. Here, we devised an AS treatment strategy based on reinstating dual-isoform expression of human UBE3A (hUBE3A) in the developing brain. Kozak sequence engineering of our codon-optimized vector (hUBE3Aopt) enabled translation of both short and long hUBE3A protein isoforms at a near-endogenous 3:1 (short/long) ratio, a feature that could help to support optimal therapeutic outcomes. To model widespread brain delivery and early postnatal onset of hUBE3A expression, we packaged the hUBE3Aopt vector into PHP.B capsids and performed intracerebroventricular injections in neonates. This treatment significantly improved motor learning and innate behaviors in AS mice, and it rendered them resilient to epileptogenesis and associated hippocampal neuropathologies induced by seizure kindling. hUBE3A overexpression occurred frequently in the hippocampus but was uncommon in the neocortex and other major brain structures; furthermore, it did not correlate with behavioral performance. Our results demonstrate the feasibility, tolerability, and therapeutic potential for dual-isoform hUBE3A gene transfer in the treatment of AS.
MeSH term(s)	Amino Acid Sequence ; Angelman Syndrome/genetics ; Animals ; Disease Models, Animal ; Humans ; Mice ; Seizures/genetics ; Treatment Outcome ; Ubiquitin-Protein Ligases
Chemical Substances	UBE3A protein, human (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.144712
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Article ; Online: Mono-ubiquitination of Rabphilin 3A by UBE3A serves a non-degradative function.

Avagliano Trezza, Rossella / Punt, A Mattijs / Mientjes, Edwin / van den Berg, Marlene / Zampeta, F Isabella / de Graaf, Ilona J / van der Weegen, Yana / Demmers, Jeroen A A / Elgersma, Ype / Distel, Ben

Scientific reports

2021 Volume 11, Issue 1, Page(s) 3007

Abstract: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by brain-specific loss of UBE3A, an E3 ubiquitin protein ligase. A substantial number of possible ubiquitination targets of UBE3A have been identified, although evidence of being ... ...

Abstract	Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by brain-specific loss of UBE3A, an E3 ubiquitin protein ligase. A substantial number of possible ubiquitination targets of UBE3A have been identified, although evidence of being direct UBE3A substrates is often lacking. Here we identified the synaptic protein Rabphilin-3a (RPH3A), an effector of the RAB3A small GTPase involved in axonal vesicle priming and docking, as a ubiquitination target of UBE3A. We found that the UBE3A and RAB3A binding sites on RPH3A partially overlap, and that RAB3A binding to RPH3A interferes with UBE3A binding. We confirmed previous observations that RPH3A levels are critically dependent on RAB3A binding but, rather surprisingly, we found that the reduced RPH3A levels in the absence of RAB3A are not mediated by UBE3A. Indeed, while we found that RPH3A is ubiquitinated in a UBE3A-dependent manner in mouse brain, UBE3A mono-ubiquitinates RPH3A and does not facilitate RPH3A degradation. Moreover, we found that an AS-linked UBE3A missense mutation in the UBE3A region that interacts with RPH3A, abrogates the interaction with RPH3A. In conclusion, our results identify RPH3A as a novel target of UBE3A and suggest that UBE3A-dependent ubiquitination of RPH3A serves a non-degradative function.
Language	English
Publishing date	2021-02-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-82319-9
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Article ; Online: Loss of nuclear UBE3A activity is the predominant cause of Angelman syndrome in individuals carrying UBE3A missense mutations.

Bossuyt, Stijn N V / Punt, A Mattijs / de Graaf, Ilona J / van den Burg, Janny / Williams, Mark G / Heussler, Helen / Elgersma, Ype / Distel, Ben

Human molecular genetics

2021 Volume 30, Issue 6, Page(s) 430–442

Abstract: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by deletion (~75%) or mutation (~10%) of the ubiquitin E3 ligase A (UBE3A) gene, which encodes a HECT type E3 ubiquitin protein ligase. Although the critical substrates of UBE3A are ... ...

Abstract	Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by deletion (~75%) or mutation (~10%) of the ubiquitin E3 ligase A (UBE3A) gene, which encodes a HECT type E3 ubiquitin protein ligase. Although the critical substrates of UBE3A are unknown, previous studies have suggested a critical role of nuclear UBE3A in AS pathophysiology. Here, we investigated to what extent UBE3A missense mutations disrupt UBE3A subcellular localization as well as catalytic activity, stability and protein folding. Our functional screen of 31 UBE3A missense mutants revealed that UBE3A mislocalization is the predominant cause of UBE3A dysfunction, accounting for 55% of the UBE3A mutations tested. The second major cause (29%) is a loss of E3-ubiquitin ligase activity, as assessed in an Escherichia coli in vivo ubiquitination assay. Mutations affecting catalytic activity are found not only in the catalytic HECT domain, but also in the N-terminal half of UBE3A, suggesting an important contribution of this N-terminal region to its catalytic potential. Together, our results show that loss of nuclear UBE3A E3 ligase activity is the predominant cause of UBE3A-linked AS. Moreover, our functional analysis screen allows rapid assessment of the pathogenicity of novel UBE3A missense variants which will be of particular importance when treatments for AS become available.
MeSH term(s)	Angelman Syndrome/genetics ; Angelman Syndrome/pathology ; Animals ; Cell Nucleus/metabolism ; Escherichia coli/metabolism ; HEK293 Cells ; Humans ; Mice ; Mutation, Missense ; Neurons/metabolism ; Saccharomyces cerevisiae/metabolism ; Ubiquitin-Protein Ligases/chemistry ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
Chemical Substances	UBE3A protein, human (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddab050
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Zs.A 3469: Show issues

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Article ; Online: A recurrent missense variant in the E3 ubiquitin ligase substrate recognition subunit FEM1B causes a rare syndromic neurodevelopmental disorder.

Lecoquierre, François / Punt, A Mattijs / Ebstein, Frédéric / Wallaard, Ilse / Verhagen, Rob / Studencka-Turski, Maja / Duffourd, Yannis / Moutton, Sébastien / Tran Mau-Them, Frédédic / Philippe, Christophe / Dean, John / Tennant, Stephen / Brooks, Alice S / van Slegtenhorst, Marjon A / Jurgens, Julie A / Barry, Brenda J / Chan, Wai-Man / England, Eleina M / Martinez Ojeda, Mayra /

Engle, Elizabeth C / Robson, Caroline D / Morrow, Michelle / Innes, A Micheil / Lamont, Ryan / Sanderson, Matthea / Krüger, Elke / Thauvin, Christel / Distel, Ben / Faivre, Laurence / Elgersma, Ype / Vitobello, Antonio

Genetics in medicine : official journal of the American College of Medical Genetics

2024 Volume 26, Issue 6, Page(s) 101119

Abstract: Purpose: Fem1 homolog B (FEM1B) acts as a substrate recognition subunit for ubiquitin ligase complexes belonging to the CULLIN 2-based E3 family. Several biological functions have been proposed for FEM1B, including a structurally resolved function as a ... ...

Abstract	Purpose: Fem1 homolog B (FEM1B) acts as a substrate recognition subunit for ubiquitin ligase complexes belonging to the CULLIN 2-based E3 family. Several biological functions have been proposed for FEM1B, including a structurally resolved function as a sensor for redox cell status by controlling mitochondrial activity, but its implication in human disease remains elusive. Methods: To understand the involvement of FEM1B in human disease, we made use of Matchmaker exchange platforms to identify individuals with de novo variants in FEM1B and performed their clinical evaluation. We performed functional validation using primary neuronal cultures and in utero electroporation assays, as well as experiments on patient's cells. Results: Five individuals with a recurrent de novo missense variant in FEM1B were identified: NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln) (FEM1B Conclusion: Overall, our data indicate that p.(Arg126Gln) induces aberrant FEM1B activation, resulting in a gain-of-function mechanism associated with a severe syndromic developmental disorder in humans.
Language	English
Publishing date	2024-03-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1455352-1
ISSN	1530-0366 ; 1098-3600
ISSN (online)	1530-0366
ISSN	1098-3600
DOI	10.1016/j.gim.2024.101119
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Zs.A 5059: Show issues

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Article ; Online: 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.

Geerts-Haages, Amber / Bossuyt, Stijn N V / den Besten, Inge / Bruggenwirth, Hennie / van der Burgt, Ineke / Yntema, Helger G / Punt, A Mattijs / Brooks, Alice / Elgersma, Ype / Distel, Ben / Valstar, Marlies

Molecular genetics & genomic medicine

2020 Volume 8, Issue 11, Page(s) e1481

Abstract: Background: Loss of functional UBE3A, an E3 protein ubiquitin ligase, causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, epilepsy, movement or balance disorder, and a ... ...

Abstract	Background: Loss of functional UBE3A, an E3 protein ubiquitin ligase, causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, epilepsy, movement or balance disorder, and a characteristic behavioral pattern. We identified a novel UBE3A sequence variant in a large family with eight affected individuals, who did not meet the clinical AS criteria. Methods: Detailed clinical examination and genetic analysis was performed to establish the phenotypic diversity and the genetic cause. The function of the mutant UBE3A protein was assessed with respect to its subcellular localization, stability, and E3 ubiquitin ligase activity. Results: All eight affected individuals showed the presence of a novel maternally inherited UBE3A sequence variant (NM_130838.4(UBE3A):c.1018-1020del, p.(Asn340del), which is in line with a genetic AS diagnosis. Although they presented with moderate to severe intellectual disability, the phenotype did not match the clinical criteria for AS. In line with this, functional analysis of the UBE3A p.Asn340del mutant protein revealed no major deficits in UBE3A protein localization, stability, or E3 ubiquitin ligase activity. Conclusion: The p.(Asn340del) mutant protein behaves distinctly different from previously described AS-linked missense mutations in UBE3A, and causes a phenotype that is markedly different from AS. This study further extends the range of phenotypes that are associated with UBE3A loss, duplication, or mutation.
MeSH term(s)	Adult ; Angelman Syndrome/diagnosis ; Angelman Syndrome/genetics ; Animals ; Developmental Disabilities/diagnosis ; Developmental Disabilities/genetics ; Diagnosis, Differential ; Enzyme Stability ; Female ; Gene Deletion ; HEK293 Cells ; Humans ; Male ; Mice ; Pedigree ; Phenotype ; Protein Transport ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	UBE3A protein, human (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2020-09-05
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2734884-2
ISSN	2324-9269 ; 2324-9269
ISSN (online)	2324-9269
ISSN	2324-9269
DOI	10.1002/mgg3.1481
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Article ; Online: Secreted retrovirus-like GAG-domain-containing protein PEG10 is regulated by UBE3A and is involved in Angelman syndrome pathophysiology.

Cell reports. Medicine

2021 Volume 2, Issue 8, Page(s) 100360

Abstract: Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of ... ...

Abstract	Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of maternal
MeSH term(s)	Angelman Syndrome/metabolism ; Angelman Syndrome/physiopathology ; Animals ; Apoptosis Regulatory Proteins/metabolism ; Cell Movement ; Child, Preschool ; DNA-Binding Proteins/metabolism ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/ultrastructure ; Female ; Gene Products, gag/chemistry ; Humans ; Induced Pluripotent Stem Cells/pathology ; Male ; Mice, Inbred C57BL ; Neurons/metabolism ; Neurons/pathology ; Proteasome Endopeptidase Complex/metabolism ; Protein Domains ; RNA-Binding Proteins/metabolism ; Retroelements/genetics ; Retroviridae/metabolism ; Stress Granules/metabolism ; Stress Granules/ultrastructure ; Transcriptome/genetics ; Ubiquitin-Protein Ligases/metabolism ; Mice
Chemical Substances	Apoptosis Regulatory Proteins ; DNA-Binding Proteins ; Gene Products, gag ; PEG10 protein, human ; RNA-Binding Proteins ; Retroelements ; UBE3A protein, human (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2021-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2021.100360
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Article ; Online: Loss of nuclear UBE3A causes electrophysiological and behavioral deficits in mice and is associated with Angelman syndrome.

Avagliano Trezza, Rossella / Sonzogni, Monica / Bossuyt, Stijn N V / Zampeta, F Isabella / Punt, A Mattijs / van den Berg, Marlene / Rotaru, Diana C / Koene, Linda M C / Munshi, Shashini T / Stedehouder, Jeffrey / Kros, Johan M / Williams, Mark / Heussler, Helen / de Vrij, Femke M S / Mientjes, Edwin J / van Woerden, Geeske M / Kushner, Steven A / Distel, Ben / Elgersma, Ype

Nature neuroscience

2019 Volume 22, Issue 8, Page(s) 1235–1247

Abstract: Mutations affecting the gene encoding the ubiquitin ligase UBE3A cause Angelman syndrome. Although most studies focus on the synaptic function of UBE3A, we show that UBE3A is highly enriched in the nucleus of mouse and human neurons. We found that the ... ...

Abstract	Mutations affecting the gene encoding the ubiquitin ligase UBE3A cause Angelman syndrome. Although most studies focus on the synaptic function of UBE3A, we show that UBE3A is highly enriched in the nucleus of mouse and human neurons. We found that the two major isoforms of UBE3A exhibit highly distinct nuclear versus cytoplasmic subcellular localization. Both isoforms undergo nuclear import through direct binding to PSMD4 (also known as S5A or RPN10), but the amino terminus of the cytoplasmic isoform prevents nuclear retention. Mice lacking the nuclear UBE3A isoform recapitulate the behavioral and electrophysiological phenotypes of Ube3a
MeSH term(s)	Angelman Syndrome/genetics ; Angelman Syndrome/psychology ; Animals ; Behavior, Animal ; Carrier Proteins/metabolism ; Cell Nucleus/enzymology ; Cell Nucleus/genetics ; Cytosol/enzymology ; Electrophysiological Phenomena/genetics ; Female ; Humans ; Isoenzymes/genetics ; Male ; Mice ; Mice, Knockout ; Mutation, Missense/genetics ; Nesting Behavior ; Neurons/enzymology ; Psychomotor Performance ; RNA-Binding Proteins ; Swimming/psychology ; Ubiquitin-Protein Ligases/genetics ; Zinc Fingers
Chemical Substances	Carrier Proteins ; Isoenzymes ; Psmd4 protein, mouse ; RNA-Binding Proteins ; Ube3a protein, mouse (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2019-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-019-0425-0
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