AUTHOR=Lu Ke , Jia Xiaodan , Wu Jiaqi , Wang Qiuling , Liang Xu-Fang 

TITLE=Neuropeptide Y receptor Y2 (npy2r) deficiency reduces anxiety and increases food intake in Japanese medaka (Oryzias latipes)

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1273006

DOI=10.3389/fcell.2023.1273006

ISSN=2296-634X

ABSTRACT=<p>Neuropeptide Y receptor Y2 (<italic>npy2r</italic>) 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 <italic>npy2r</italic> has the similar function in fish as in mammals. In this study, we used the CRISPR/Cas9 system to establish <italic>npy2r</italic>-deficient medaka (<italic>Oryzias latipes</italic>). Unexpectedly, the deletion of <italic>npy2r</italic> resulted in the <italic>npy2r</italic><sup><italic>+/−</italic></sup> medaka were all-male, therefore, <italic>npy2r</italic> homozygous mutant lines could not be established. The deletion of <italic>npy2r</italic> increased the food intake in medaka, and the expression levels of appetite stimulating genes (<italic>agrp</italic>, <italic>npy</italic>) increased significantly, while the expression levels of anorexia factors (<italic>cck</italic>, <italic>pomc</italic>) decreased significantly. Moreover, the absence of <italic>npy2r</italic> significantly increased the total length and body weight of medaka. The mirror test and open field test showed that <italic>npy2r</italic><sup><italic>+/−</italic></sup> medaka improved sociability and reduced anxiety-like behavior, qRT-PCR analysis showed that the expression levels of anxiety related genes (<italic>th1</italic>, <italic>th2</italic>, <italic>gr1</italic>, <italic>gr2</italic>, and <italic>mr</italic>) in <italic>npy2r</italic><sup><italic>+/−</italic></sup> medaka were significantly decreased. So far, this is the first <italic>npy2r</italic> gene knockout model established in fish and demonstrates that <italic>npy2r</italic> plays an important role in the regulation of reproduction, feeding and anxiety in fish.</p>