Gpr180-flox Mouse

Gpr180, also known as intimal thickness-related receptor (ITR), is a protein that belongs to the Golgi-dynamics domain seven-transmembrane helix (GOST) protein family [4,6]. It is involved in multiple biological functions, including regulating thermogenic adipocyte function, lipid metabolism, and signal transduction during gametogenesis in Plasmodium. It is associated with the TGFβ signalling pathway and also impacts the regulation of smooth muscle cell growth [1,7,8,9]. Genetic models, such as knockout mice, have been crucial for studying its functions.

In adipocytes, Gpr180 knockout mice show exacerbated lipid metabolism disorders induced by a high-fat diet (HFD), indicating that Gpr180 suppresses lipid accumulation by inhibiting lipogenesis and fatty acid uptake [2]. In hepatic studies, Gpr180 knockout mice have ameliorated hepatic and plasma lipid levels without influencing glucose metabolism after HFD intake, achieved through down-regulation of mTORC1 signaling [3]. Additionally, hepatic Gpr180 deficiency in mice decreases triglyceride and cholesterol contents in the liver and plasma, ameliorates hepatic lipid deposition, increases energy metabolism, and reduces adiposity, acting via the Gi-PKA-SREBP pathway [5]. In Plasmodium berghei, knockout of pbgpr180 impairs gamete formation and reduces parasite transmission to mosquitoes, suggesting Gpr180's role in the cGMP-protein kinase G-Ca2+ signaling pathway during gametogenesis [7].

In conclusion, Gpr180 plays essential roles in lipid metabolism, both in adipocytes and the liver, and in malaria parasite transmission. The use of Gpr180 knockout mouse models has provided valuable insights into its functions in lipid-related metabolic diseases and malaria parasite development, potentially offering new therapeutic targets for these conditions [2,3,5,7].