Autism spectrum disorder (ASD) is a heterogeneously childhood neurodevelopmental disorder, believed to be under development of various genetic and environmental factors. Autophagy and related pathways have also been implicated in the etiology of ASD. We aimed to investigate autophagic markers by generating the transgenerational inheritance of ASD-like behaviors in the Cc2d1a animal model of ASD. Cc2d1a (+/−) mouse model of ASD was built in two different groups by following three generations. After behavior test, bilateral hippocampus was sliced. Western Blot assay and quantitative real-time polymerase chain reaction (QRT-PCR) were used for measurement of LC3 and Beclin-1 as key regulators of autophagy. All of the animal and laboratory studies were conducted in the Erciyes University Genome and Stem Cell Center (GENKOK). Significant LC3 and Beclin-1 mRNA expression levels were observed in mouse hippocampus between groups and generations. Western blot confirmed the changes of the proteins in the hippocampus. LC3 expressions were increased for females and decreased for males compared to the control group. Beclin-1 expression levels were found to be significantly decreased in males and females compared to controls. This study could help explain a new pathway of autophagy in ASD mouse models. Future animal studies need to investigate sex differences in mouse modeling autism-relevant genes like CC2D1A. We anticipate our results to be a starting point for more comprehensive autophagy studies in this mouse model of ASD.

中文翻译：

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自噬在自闭症的跨代Cc2d1a小鼠模型中的自噬失调。

自闭症谱系障碍（ASD）是儿童期的异质性神经发育障碍，据信正在各种遗传和环境因素的影响下发展。自噬和相关途径也与ASD的病因有关。我们旨在通过在ASD的Cc2d1a动物模型中产生类似ASD行为的跨代遗传来研究自噬标记。Cc2d1a通过以下三代，将ASD的（+/-）小鼠模型分为两个不同的组。行为测试后，将双侧海马切成薄片。Western Blot分析和定量实时聚合酶链反应（QRT-PCR）用于测量LC3和Beclin-1作为自噬的关键调节剂。所有动物和实验室研究均在Erciyes大学基因组和干细胞中心（GENKOK）中进行。重要的LC3和Beclin - 1组和代之间在小鼠海马中观察到mRNA表达水平。Western印迹证实了海马中蛋白质的变化。与对照组相比，女性的LC3表达增加，而男性则降低。与对照相比，发现男性和女性中Beclin-1表达水平显着降低。这项研究可能有助于解释ASD小鼠模型中自噬的新途径。未来的动物研究需要调查与CC2D1A等自闭症相关的小鼠模型中的性别差异。我们预计我们的结果将成为此ASD小鼠模型中更全面的自噬研究的起点。