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...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Journal of Neurodevelopmental Disorders |
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| Online Access: | http://link.springer.com/article/10.1186/s11689-020-09319-0 |
| _version_ | 1828471158319611904 |
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| author | Nicole Martin-Kenny Nathalie G. Bérubé |
| author_facet | Nicole Martin-Kenny Nathalie G. Bérubé |
| author_sort | Nicole Martin-Kenny |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T05:06:13Z |
| format | Article |
| id | doaj.art-bcb2c66f020b4ae1ac947fb682503047 |
| institution | Directory Open Access Journal |
| issn | 1866-1947 1866-1955 |
| language | English |
| last_indexed | 2024-12-11T05:06:13Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-bcb2c66f020b4ae1ac947fb6825030472022-12-22T01:20:01ZengBMCJournal of Neurodevelopmental Disorders1866-19471866-19552020-06-0112111110.1186/s11689-020-09319-0Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female miceNicole Martin-Kenny0Nathalie G. Bérubé1Department of Paediatrics, Schulich School of Medicine and Dentistry, Western UniversityDepartment of Paediatrics, Schulich School of Medicine and Dentistry, Western UniversityAbstract 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.http://link.springer.com/article/10.1186/s11689-020-09319-0Autism spectrum disorderATRXSocial behavioursRepetitive behavioursStartle responseGenetically engineered mice |
| spellingShingle | Nicole Martin-Kenny Nathalie G. Bérubé Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice Journal of Neurodevelopmental Disorders Autism spectrum disorder ATRX Social behaviours Repetitive behaviours Startle response Genetically engineered mice |
| title | Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice |
| title_full | Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice |
| title_fullStr | Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice |
| title_full_unstemmed | Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice |
| title_short | Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice |
| title_sort | effects of a postnatal atrx conditional knockout in neurons on autism like behaviours in male and female mice |
| topic | Autism spectrum disorder ATRX Social behaviours Repetitive behaviours Startle response Genetically engineered mice |
| url | http://link.springer.com/article/10.1186/s11689-020-09319-0 |
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