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Mutation of ube3a causes developmental abnormalities and autism-like molecular and behavioral alterations in zebrafish

2025· article· en· W4414147015 on OpenAlexaff
Godfried Dougnon, Lana Rummel, Hideaki Matsui

Bibliographic record

VenueBrain Research Bulletin · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsUniversity of Victoria
FundersJapan Society for the Promotion of ScienceJapan Agency for Medical Research and DevelopmentNiigata UniversityTakeda Science Foundation
KeywordsUBE3AZebrafishAngelman syndromeNeurodevelopmental disorderMutationExonPoint mutationModel organism

Abstract

fetched live from OpenAlex

Mutations in the UBE3A gene are responsible for neurodevelopmental disorders (NDDs), including Angelman syndrome (AS), which is characterized by developmental delays, impaired motor coordination, and cognitive disabilities. In recent years, UBE3A mutations have also been linked to autism spectrum disorders (ASD), due to their significant role in synaptic plasticity and cognitive function. Although substantial research has utilized mammalian models, the zebrafish (Danio rerio) provides unique opportunities to investigate gene functions owing to their transparent embryos, rapid development, and suitability for large-scale genetic and behavioral studies. In this study, we characterized a zebrafish model harboring a point mutation (T > A) in exon 3 of the zebrafish ube3a gene, which induces a stop codon resulting in a truncated protein. We performed comprehensive developmental, behavioral, and molecular analyses to investigate the impact of Ube3a dysfunction at both larval and adult stages. We observed alterations in embryonic development, significant locomotor deficits, including stereotypic movements, and reduced social preference and aggressiveness. Furthermore, RNA sequencing analysis of both larvae and adults revealed dysregulation in chromatin, nucleosome, protein-DNA, and primary cilia-related genes. Our findings provide a functional characterization of the ube3a mutation in zebrafish at both larval and adult stages. This zebrafish model offers new insights into the roles of UBE3A in neurodevelopment and behavior, expanding our understanding of its dysfunction in NDDs.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.268
Threshold uncertainty score0.408

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.028
GPT teacher head0.362
Teacher spread0.334 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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