Testosterone interrupts binding of Neurexin and Neuroligin that are expressed in a highly socialized rodent, Octodon degus
Testosterone interrupts binding of Neurexin and Neuroligin that are expressed in a highly socialized rodent, Octodon degus
复制标题
睾丸激素会中断高度社会化的啮齿动物八齿鼠中表达的 Neurexin 和 Neuroligin 的结合
DOI：
10.1016/j.bbrc.2021.03.015
复制
发表时间：
2021
影响因子：
3.1
通讯作者：
Yagishita Sosuke
中科院分区：
文献类型：
--
作者：
Yagishita-Kyo Nan;Ikai Yuki;Uekita Tomoko;Shinohara Akio;Koshimoto Chihiro;Yoshikawa Keisuke;Maruyama Kei;Yagishita Sosuke
Ocdon degusis被认为是最像人类的啮齿动物之一，因为它的认知功能得到了改善。针对其高度的社会性，我们克隆并鉴定了一些与其社会性相关的基因，以期在分子生物学中建立一个高度社会化的动物模型。我们克隆了与人类自闭症谱系障碍相关的社会性相关基因--Degus Neurexin和Neurolinin。根据我们的结果，脑组织表达的Neuresin和Neuroigin的氨基酸序列与人类的序列高度保守。最值得注意的是，DECUUS神经连接蛋白4与人类神经连接蛋白4X高度相似，而人类神经连接蛋白4X是最重要的自闭症相关基因之一，而小鼠神经连接蛋白4与人类神经连接蛋白4X的相似性较低。此外，我们的工作还表明，睾酮直接与神经尿素素结合，并截断细胞间的神经尿素素-神经连接蛋白结合。此外，令人高度感兴趣的是，睾丸激素是男性自闭症发病率较高的另一个关键分子。这些结果表明，地塞米松有可能成为社交动物模型，并可能进一步促进对自闭症发病机制的理解。
Octodon degusis said to be one of the most human-like rodents because of its improved cognitive function. Focusing on its high sociality, we cloned and characterized some sociality-related genes ofdegus, in order to establishdegusas a highly socialized animal model in molecular biology. We cloneddegus NeurexinandNeuroliginas sociality-related genes, which are genetically related to autism spectrum disorder in human. According to our results, amino acid sequences of Neurexin and Neuroligin expressed indegusbrain, are highly conserved to that of human sequences. Most notably,degusNeuroligin4 is highly similar to human Neuroligin4X, which is one of the most important autism-related genes, whereas mouse Neuroligin4 is known to be poorly similar to human Neuroligin4X. Furthermore, our work also indicated that testosterone directly binds todegusNeurexin and intercepts intercellular Neurexin-Neuroligin binding. Moreover, it is of high interest that testosterone is another key molecule of the higher incidence of autism in male. These results indicated thatdegushas the potential for animal model of sociality, and furthermore may promote understanding toward the pathogenic mechanism of autism.