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Updated: Jul 11, 2025
Strategies for Assessing Autistic-Like Behaviors in Mice
Published on: September 20, 2024
A mouse model of ATRX deficiency with cognitive deficits and autistic traits
Katherine M Quesnel1,2,3, Nicole Martin-Kenny1,2,3, Nathalie G Bérubé4,5,6,7
1Department of Anatomy & Cell Biology, Western University, London, Canada.
Background:
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, but no apparent autistic-like behaviours.
Methods:
We generated mice with an earlier embryonic deletion of ATRX in forebrain excitatory neurons and characterized their behaviour using a series of memory and autistic-related paradigms.
Results:
We found that mutant mice displayed a broader spectrum of impairments, including fear memory, decreased anxiety-like behaviour, hyperactivity, as well as self-injurious and repetitive grooming. Sex-specific alterations were also observed, including male-specific aggression, sensory gating impairments, and decreased social memory.
Conclusions:
Collectively, the findings indicate that early developmental abnormalities arising from ATRX deficiency in forebrain excitatory neurons contribute to the presentation of fear memory deficits as well as autistic-like behaviours.
