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Record W4384943166 · doi:10.1101/2023.07.19.549759

A mouse model of ATRX deficiency with cognitive deficits and autistic traits

2023· preprint· en· W4384943166 on OpenAlexafffund
Katherine M Quesnel, Nicole Martin‐Kenny, Nathalie G. Bérubé

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsChildren’s Health Research InstituteWestern University
FundersRobarts Research InstituteCanada First Research Excellence Fund
KeywordsATRXNeuroscienceAutismForebrainPsychologyHaploinsufficiencyEpigeneticsBiologyDevelopmental psychologyGeneGeneticsCentral nervous systemMutationPhenotype

Abstract

fetched live from OpenAlex

ABSTRACT ATRX is an ATP-dependent chromatin remodeling protein with essential roles in safeguarding genome integrity and modulating gene expression. Deficiencies in this protein cause ATR-X syndrome, a condition characterized by intellectual disability and an array of developmental abnormalities, including features of autism. Previous studies demonstrated that deleting ATRX in mouse forebrain excitatory neurons postnatally resulted in male-specific memory deficits. Here, we introduce a new model where ATRX is deleted at earlier embryonic stages, resulting in a broader spectrum of impairments, including contextual fear memory deficits, decreased anxiety, hyperactivity, as well as self-injurious and stereotyped behaviours. Sex-specific alterations were also observed, with males displaying heightened aggression and impaired sensory gating, while females exhibit social avoidance. Collectively, the findings indicate that early developmental abnormalities arising from ATRX deficiency in neurons contribute to of the presentation of autistic-like behaviours. Summary Statement Mice with embryonic loss of ATRX in excitatory neurons represent a clinically relevant model to study sexually dimorphic alterations in cognitive and autistic traits.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0030.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0050.001

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 head0.017
GPT teacher head0.213
Teacher spread0.196 · 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 source (direct Gemma or distilled Codex), 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
Published2023
Admission routes2
Has abstractyes

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