AUTHOR=Lee Soo Yeon , Kweon Hanseul , Kang Hyojin , Kim Eunjoon 

TITLE=Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=15

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.1022306

DOI=10.3389/fnmol.2022.1022306

ISSN=1662-5099

ABSTRACT=<p>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. <italic>Chd8</italic>-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 <italic>Chd8</italic> mutations remains unknown. In addition, it remains unclear whether sexually dimorphic phenotypes in <italic>Chd8</italic>-mutant mice are differentially observed in males and females across different ages. We here generated new <italic>Chd8</italic>-mutant (knock-in) mice carrying a patient-derived mutation causing an N-terminal and stronger protein truncation (<italic>Chd8<sup>+/S62X</sup></italic> mice) and characterized the mice by behavioral analyses. Juvenile <italic>Chd8<sup>+/S62X</sup></italic> mice displayed male-preponderant autistic-like behaviors; hypoactivity and enhanced mother-seeking/attachment behavior in males but not in females. Adult male and female <italic>Chd8<sup>+/S62X</sup></italic> 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 <italic>Chd8</italic> mutations (N2373K and S62X).</p>