Srancikova Annamaria, Reichova Alexandra, Bacova Zuzana, Bakos Jan
Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Institute of Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
Endocr Regul. 2021 Dec 7;55(4):234-237. doi: 10.2478/enr-2021-0025.
The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 ()-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms. DNA methyltransferases (DNMTs), which modulate several cellular processes in neurodevelopment, are implicated in the pathophysiology of autism. In this study, we aimed to describe the gene expression changes of major in the brain of -deficient mice during early development. The gene expression was analyzed by qPCR in 5-day-old homo-zygous -deficient mice. We found significantly lower and gene expression levels in the frontal cortex. However, no such changes were observed in the hippocampus. However, significant increase was observed in the expression of and genes in the hypothalamus of -deficient mice. The present data indicate that abnormalities in the gene are accompanied by an altered expression of DNA methylation enzymes in the early brain development stages, therefore, specific epigenetic control mechanisms in autism-relevant models should be more extensively investigated.
DNA甲基化与去甲基化之间的平衡对于大脑发育至关重要。因此，控制DNA甲基化模式的酶的表达改变可能会导致包括自闭症在内的神经发育障碍的病因。SH3和多个锚蛋白重复结构域3（SHANK3）缺陷小鼠通常被用作一种特征明确的转基因模型来研究自闭症症状的分子机制。DNA甲基转移酶（DNMTs）在神经发育中调节多种细胞过程，与自闭症的病理生理学有关。在本研究中，我们旨在描述SHANK3缺陷小鼠早期发育过程中大脑中主要DNA甲基转移酶的基因表达变化。通过qPCR分析了5日龄纯合SHANK3缺陷小鼠的DNA甲基转移酶基因表达。我们发现额叶皮质中DNMT1和DNMT3a的基因表达水平显著降低。然而，在海马体中未观察到此类变化。然而，在SHANK3缺陷小鼠的下丘脑，DNMT3b和TET1基因的表达显著增加。目前的数据表明，在大脑发育早期阶段，SHANK3基因异常伴随着DNA甲基化酶表达的改变，因此，应更广泛地研究自闭症相关模型中的特定表观遗传控制机制。
