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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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Autores principales: Lee, Soo Yeon, Kweon, Hanseul, Kang, Hyojin, Kim, Eunjoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641250/
https://www.ncbi.nlm.nih.gov/pubmed/36385756
http://dx.doi.org/10.3389/fnmol.2022.1022306
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author Lee, Soo Yeon
Kweon, Hanseul
Kang, Hyojin
Kim, Eunjoon
author_facet Lee, Soo Yeon
Kweon, Hanseul
Kang, Hyojin
Kim, Eunjoon
author_sort Lee, Soo Yeon
collection PubMed
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).
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spelling pubmed-96412502022-11-15 Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors Lee, Soo Yeon Kweon, Hanseul Kang, Hyojin Kim, Eunjoon Front Mol Neurosci Molecular Neuroscience 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). Frontiers Media S.A. 2022-10-25 /pmc/articles/PMC9641250/ /pubmed/36385756 http://dx.doi.org/10.3389/fnmol.2022.1022306 Text en Copyright © 2022 Lee, Kweon, Kang and Kim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Lee, Soo Yeon
Kweon, Hanseul
Kang, Hyojin
Kim, Eunjoon
Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors
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 Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641250/
https://www.ncbi.nlm.nih.gov/pubmed/36385756
http://dx.doi.org/10.3389/fnmol.2022.1022306
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