Abstract
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.