Ebrahimiazar Sara, Kikkawa Takako, Minakuchi Yohei, Miyashita Satoshi, Manabe Shyu, Hoshino Mikio, Toyoda Atsushi, Osumi Noriko
Department of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan.
Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka, 411-8540, Japan.
Sci Data. 2025 Jun 2;12(1):927. doi: 10.1038/s41597-025-05104-7.
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene. FXS patients exhibit autistic behaviors and abnormal brain structures, with notable sex differences. However, the mechanisms by which Fmr1 deficiency leads to these sex differences during brain development remain unclear. In this study, we performed bulk RNA sequencing on telencephalon samples of Fmr1-knockout mice of both sexes at embryonic day (E) 14.5, i.e., at the peak of neurogenesis. Clustering analysis revealed gene expression differences influenced by Fmr1 gene dosage and sex. We found that majority of the transcripts were shared between male and female sample groups, while a smaller number were unique to each sex. Our dataset underscores the importance of studying brain development during the embryonic period to detect sex-dependent genetic factors which contribute to neurodevelopmental disorders.
脆性X综合征(FXS)是一种由脆性X信使核糖核蛋白1(FMR1)基因突变引起的神经发育障碍。FXS患者表现出自闭行为和异常的脑结构,且存在显著的性别差异。然而,Fmr1基因缺陷在大脑发育过程中导致这些性别差异的机制仍不清楚。在本研究中,我们对胚胎期第14.5天(E14.5),即神经发生高峰期的雌雄Fmr1基因敲除小鼠的端脑样本进行了批量RNA测序。聚类分析揭示了受Fmr1基因剂量和性别影响的基因表达差异。我们发现,大多数转录本在雄性和雌性样本组之间共享,而每个性别特有的转录本数量较少。我们的数据集强调了在胚胎期研究大脑发育以检测导致神经发育障碍的性别依赖性遗传因素的重要性。