Neuropeptide Y receptor Y8b () regulates feeding and digestion in Japanese medaka () larvae: evidence from gene knockout.

Neuropeptide Y receptor Y8 (NPY8R) is a fish-specific receptor with two subtypes, NPY8AR and NPY8BR. Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that NPY8BR plays an important role in feeding regulation; this has been found in only a few fish, at present. In order to better understand the physiological function of , especially in digestion, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate Japanese medaka (). We found that the deletion of in medaka larvae affected their feeding and digestion ability, ultimately affecting their growth. Specifically, deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes ( and ). medaka larvae fed for 10 d (10th day of feeding) still had incompletely digested brine shrimp () in the digestive tract 8 h after feeding, the messenger RNA (mRNA) expression levels of digestion-related genes (, , , and ) were significantly decreased, and the activity of amylase, trypsin, and lipase also significantly decreased. The deletion of in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes ( and ). Hematoxylin and eosin (H&E) sections of intestinal tissue showed that medaka larvae had damaged intestine, thinned intestinal wall, and shortened intestinal villi. So far, this is the first gene knockout model established in fish and the first demonstration that plays an important role in digestion.