Patatin-like phospholipase domain containing 5 （PNPLA5） is a neotype neutral lipase with dual activity of anabolism and catabolism in vitro and in vivo, which has a low mRNA expression level in humans and mice. PNPL...Patatin-like phospholipase domain containing 5 （PNPLA5） is a neotype neutral lipase with dual activity of anabolism and catabolism in vitro and in vivo, which has a low mRNA expression level in humans and mice. PNPLA5, which is localized to lipid droplets and required for efficient autophagy by optimal initiation, has been speculated to possess triglyceride hydro- lase activity, and has been associated with low density lipoprotein cholesterol （LDL-C）. Above all, PNPLA5 is a relatively new gene, which is reported less about its biological function research, especially the function research in the rats is still blank. In this study, we examined the spatiotemporal expression profile of PNPLA5 and found that it was expressed at low levels in most organs of Sprague Dawley （SD） rats, but was present at very high levels in the skin and testes. To furth.er determine the biological function of PNPLA5 in mammals, we generated PNPLA5-knockout SD rats using the clustered regularly-interspaced short palindromic repeats （CRISPR）/Cas9 system. PNPLA5-null rats were viable, but showed a variety of phenotypic abnormalities, such as abnormal bleeding, and varied hematobiochemical parameters including increased serum total cholesterol （TC）, tdglycerides and high density lipoprotein cholesterol （HDL-C） level, and reduced LDL-C level, compared with wild-type control rats. These data are consistent with an important role for PNPLA5 in lipid metabolism, provJdJng a new target gene and animal model for treatment of cardiovascular diseases in the future.展开更多
基金funded by the National Natural Science Foundation of China(31572378)the Major National Scientific Research Projects,China(2015CB943101)the Agricultural Science and Technology Innovation Program,China(ASTIP-IAS05)
文摘Patatin-like phospholipase domain containing 5 （PNPLA5） is a neotype neutral lipase with dual activity of anabolism and catabolism in vitro and in vivo, which has a low mRNA expression level in humans and mice. PNPLA5, which is localized to lipid droplets and required for efficient autophagy by optimal initiation, has been speculated to possess triglyceride hydro- lase activity, and has been associated with low density lipoprotein cholesterol （LDL-C）. Above all, PNPLA5 is a relatively new gene, which is reported less about its biological function research, especially the function research in the rats is still blank. In this study, we examined the spatiotemporal expression profile of PNPLA5 and found that it was expressed at low levels in most organs of Sprague Dawley （SD） rats, but was present at very high levels in the skin and testes. To furth.er determine the biological function of PNPLA5 in mammals, we generated PNPLA5-knockout SD rats using the clustered regularly-interspaced short palindromic repeats （CRISPR）/Cas9 system. PNPLA5-null rats were viable, but showed a variety of phenotypic abnormalities, such as abnormal bleeding, and varied hematobiochemical parameters including increased serum total cholesterol （TC）, tdglycerides and high density lipoprotein cholesterol （HDL-C） level, and reduced LDL-C level, compared with wild-type control rats. These data are consistent with an important role for PNPLA5 in lipid metabolism, provJdJng a new target gene and animal model for treatment of cardiovascular diseases in the future.
