Flvcr1-flox Mouse

FLVCR1, or feline leukemia virus subgroup C cellular receptor 1, is a key plasma-membrane transporter in mammals. It plays a crucial role in choline metabolism as it transports extracellular choline into cells, initiating the Kennedy pathway for the synthesis of phosphatidylcholine, one of the most abundant phospholipids in mammalian cells [1,2]. Mutations in FLVCR1 have been associated with the neurodegenerative syndrome posterior column ataxia and retinitis pigmentosa [2].

Loss-of-function studies have provided significant insights into FLVCR1's role. In human cells, loss of FLVCR1 strongly impairs choline metabolism due to inhibited choline import [1]. Cells lacking FLVCR1 exhibit mitochondrial structural defects and upregulate the integrated stress response through heme-regulated inhibitor kinase [1]. Flvcr1 knockout mice are embryonic lethal, but this lethality can be partially rescued by choline supplementation, highlighting the essential role of FLVCR1-mediated choline transport in embryonic development [1]. In addition, in esophageal squamous cell carcinoma, knockdown of FLVCR1 inhibits cell proliferation, colony formation, migration, and invasion, and represses tumorigenicity and metastasis in vivo, suggesting its role in cancer progression [3].

In conclusion, FLVCR1 is essential for choline metabolism and normal embryonic development as demonstrated by knockout mouse models. Its role in cancer progression, such as in esophageal squamous cell carcinoma, further emphasizes its significance in disease-related biological processes. Understanding FLVCR1 function provides potential therapeutic targets for diseases associated with choline metabolism disorders and certain cancers.