Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors
Autism spectrum disorders (ASD) are ~4-times more common in males than females, and CHD8 (a chromatin remodeler)-related ASD shows a strong male bias (~4:1), although the underlying mechanism remains unclear. Chd8-mutant mice with a C-terminal protein-truncating mutation (N2373K) display male-prepon...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1022306/full |
| _version_ | 1811338399050629120 |
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| author | Soo Yeon Lee Hanseul Kweon Hyojin Kang Eunjoon Kim Eunjoon Kim |
| author_facet | Soo Yeon Lee Hanseul Kweon Hyojin Kang Eunjoon Kim Eunjoon Kim |
| author_sort | Soo Yeon Lee |
| collection | DOAJ |
| description | Autism spectrum disorders (ASD) are ~4-times more common in males than females, and CHD8 (a chromatin remodeler)-related ASD shows a strong male bias (~4:1), although the underlying mechanism remains unclear. Chd8-mutant mice with a C-terminal protein-truncating mutation (N2373K) display male-preponderant behavioral deficits as juveniles and adults, although whether this also applies to other Chd8 mutations remains unknown. In addition, it remains unclear whether sexually dimorphic phenotypes in Chd8-mutant mice are differentially observed in males and females across different ages. We here generated new Chd8-mutant (knock-in) mice carrying a patient-derived mutation causing an N-terminal and stronger protein truncation (Chd8+/S62X mice) and characterized the mice by behavioral analyses. Juvenile Chd8+/S62X mice displayed male-preponderant autistic-like behaviors; hypoactivity and enhanced mother-seeking/attachment behavior in males but not in females. Adult male and female Chd8+/S62X mice showed largely similar deficits in repetitive and anxiety-like behavioral domains. Therefore, the CHD8-S62X mutation induces ASD-like behaviors in juvenile male mice and adult male and female mice, pointing to an age-differential sexual dimorphism and also distinct sexual dimorphisms in different Chd8 mutations (N2373K and S62X). |
| first_indexed | 2024-04-13T18:10:11Z |
| format | Article |
| id | doaj.art-54a5d67f5b9f449095e686765262dcd7 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T18:10:11Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-54a5d67f5b9f449095e686765262dcd72022-12-22T02:35:56ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-10-011510.3389/fnmol.2022.10223061022306Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviorsSoo Yeon Lee0Hanseul Kweon1Hyojin Kang2Eunjoon Kim3Eunjoon Kim4Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, South KoreaCenter for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, South KoreaDivision of National Supercomputing, Korea Institute of Science and Technology Information, Daejeon, South KoreaDepartment of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, South KoreaCenter for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, South KoreaAutism spectrum disorders (ASD) are ~4-times more common in males than females, and CHD8 (a chromatin remodeler)-related ASD shows a strong male bias (~4:1), although the underlying mechanism remains unclear. Chd8-mutant mice with a C-terminal protein-truncating mutation (N2373K) display male-preponderant behavioral deficits as juveniles and adults, although whether this also applies to other Chd8 mutations remains unknown. In addition, it remains unclear whether sexually dimorphic phenotypes in Chd8-mutant mice are differentially observed in males and females across different ages. We here generated new Chd8-mutant (knock-in) mice carrying a patient-derived mutation causing an N-terminal and stronger protein truncation (Chd8+/S62X mice) and characterized the mice by behavioral analyses. Juvenile Chd8+/S62X mice displayed male-preponderant autistic-like behaviors; hypoactivity and enhanced mother-seeking/attachment behavior in males but not in females. Adult male and female Chd8+/S62X mice showed largely similar deficits in repetitive and anxiety-like behavioral domains. Therefore, the CHD8-S62X mutation induces ASD-like behaviors in juvenile male mice and adult male and female mice, pointing to an age-differential sexual dimorphism and also distinct sexual dimorphisms in different Chd8 mutations (N2373K and S62X).https://www.frontiersin.org/articles/10.3389/fnmol.2022.1022306/fullautism spectrum disordersCHD8mouse model of ASDchromatin remodelingsexual dimorphismage dependence |
| spellingShingle | Soo Yeon Lee Hanseul Kweon Hyojin Kang Eunjoon Kim Eunjoon Kim Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors Frontiers in Molecular Neuroscience autism spectrum disorders CHD8 mouse model of ASD chromatin remodeling sexual dimorphism age dependence |
| title | Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors |
| title_full | Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors |
| title_fullStr | Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors |
| title_full_unstemmed | Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors |
| title_short | Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors |
| title_sort | age differential sexual dimorphism in chd8 s62x mutant mouse behaviors |
| topic | autism spectrum disorders CHD8 mouse model of ASD chromatin remodeling sexual dimorphism age dependence |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1022306/full |
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