Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice.

Abstract

BACKGROUND:

Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours.

METHODS:

Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the control of the αCaMKII gene promoter. These mice were tested in a battery of behavioural tests that assess autistic-like features. We utilized paradigms that measure social behaviour, repetitive, and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak's multiple comparison test or unpaired Student's t tests as indicated.

RESULTS:

The behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits.

CONCLUSION:

The postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice.

• Authors: Nicole Martin-Kenny, Nathalie G Bérubé
• Journal: Journal of neurodevelopmental disorders (J Neurodev Disord) Vol. 12 Issue 1 Pg. 17 (06 24 2020) ISSN: 1866-1955 [Electronic] England
• PMID: 32580781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Atrx protein, mouse
• X-linked Nuclear Protein

Topics

• Animals
• Autistic Disorder (genetics)
• Chromatin Assembly and Disassembly
• Female
• Male
• Mental Retardation, X-Linked (genetics)
• Mice
• Mice, Knockout
• Mutation
• Neurons (metabolism)
• Postpartum Period
• X-linked Nuclear Protein
• alpha-Thalassemia (genetics)