Lu Ke, Jia Xiaodan, Wu Jiaqi, Wang Qiuling, Liang Xu-Fang
College of Fisheries, Chinese Perch Research Center, Huazhong Agricultural University, Wuhan, China.
Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan, China.
Front Cell Dev Biol. 2023 Nov 7;11:1273006. doi: 10.3389/fcell.2023.1273006. eCollection 2023.
Neuropeptide Y receptor Y2 () is an important receptor gene involved in anxiety and feeding regulation in mammals. Since NPY receptors have different receptor gene deletions in mammals and teleost fish, it is not clear whether has the similar function in fish as in mammals. In this study, we used the CRISPR/Cas9 system to establish -deficient medaka (). Unexpectedly, the deletion of resulted in the medaka were all-male, therefore, homozygous mutant lines could not be established. The deletion of increased the food intake in medaka, and the expression levels of appetite stimulating genes (, ) increased significantly, while the expression levels of anorexia factors (, ) decreased significantly. Moreover, the absence of significantly increased the total length and body weight of medaka. The mirror test and open field test showed that medaka improved sociability and reduced anxiety-like behavior, qRT-PCR analysis showed that the expression levels of anxiety related genes (, , , , and ) in medaka were significantly decreased. So far, this is the first gene knockout model established in fish and demonstrates that plays an important role in the regulation of reproduction, feeding and anxiety in fish.
神经肽Y受体Y2()是参与哺乳动物焦虑和摄食调节的重要受体基因。由于NPY受体在哺乳动物和硬骨鱼中有不同的受体基因缺失,尚不清楚在鱼类中是否具有与哺乳动物相似的功能。在本研究中,我们使用CRISPR/Cas9系统建立了缺失的青鳉()。出乎意料的是,的缺失导致青鳉全部为雄性,因此,无法建立纯合突变系。的缺失增加了青鳉的食物摄入量,食欲刺激基因(,)的表达水平显著增加,而厌食因子(,)的表达水平显著降低。此外,的缺失显著增加了青鳉的全长和体重。镜像测试和旷场测试表明,缺失的青鳉改善了社交能力并减少了焦虑样行为,qRT-PCR分析表明,缺失的青鳉中焦虑相关基因(,,,,和)的表达水平显著降低。到目前为止,这是在鱼类中建立的第一个基因敲除模型,证明在鱼类的繁殖、摄食和焦虑调节中起重要作用。