Abstract：
Fragile X syndrome (FXS) is the most common single gene disorder contributing to autism spectrum disorder (ASD). Although significant sex differences are observed in FXS, few studies have focused on the phenotypic characteristics as well as the differences in brain pathological changes and gene expression in FXS by sex. Therefore, we analyzed sex differences in autism-like behavior and dendritic spine development in two-month-old male and female Fmr1 KO and C57 mice and evaluated the mechanisms at transcriptome level. Results suggest that Fmr1 KO mice display sex differences in autism-like behavior and dendritic spine density. Compared to females, male had more severe effects on anxiety, repetitive stereotype-like behaviors, and socializing, with higher dendritic spine density. Furthermore, two male-biased and five female-biased expressed genes were screened based on KEGG pathway enrichment and protein-protein interaction (PPI) analyses. In conclusion, our findings show mutations in the Fmr1 gene lead to aberrant expression of related genes and affect the sex-differentiated behavioral phenotypes of Fmr1 KO mice by affecting brain development and functional architecture, and suggest future studies should focus on including female subjects to comprehensively reflect the differentiation of FXS in both sexes and develop more precise and effective therapeutic strategies.
摘要：
脆性X综合征（FXS）是导致自闭症谱系障碍（ASD）的最常见的单基因疾病。虽然在FXS中观察到显著的性别差异，很少有研究集中在FXS的表型特征以及不同性别的脑病理改变和基因表达的差异上。因此,我们分析了2个月大的雄性和雌性Fmr1KO和C57小鼠在自闭症样行为和树突状脊柱发育方面的性别差异,并在转录组水平评估了机制.结果表明，Fmr1KO小鼠在自闭症样行为和树突状脊柱密度方面表现出性别差异。与女性相比，男性对焦虑有更严重的影响，重复的刻板印象样的行为，和社交，具有较高的树突脊柱密度。此外，基于KEGG途径富集和蛋白-蛋白相互作用(PPI)分析,筛选了2个男性偏倚和5个女性偏倚表达基因.总之,我们的研究结果表明，Fmr1基因的突变导致相关基因的异常表达，并通过影响大脑发育和功能结构来影响Fmr1KO小鼠的性别分化行为表型，并建议未来的研究应侧重于纳入女性受试者，以全面反映FXS在两性中的分化，并制定更精确和有效的治疗策略。
