Cers2-flox Mouse

Cers2, encoding ceramide synthase 2, is crucial for the biosynthesis of very-long-chain (VLC) ceramides (C20-C26). VLC ceramides are part of the sphingolipid metabolism pathway, which is vital in various biological processes, including cell signaling, apoptosis, and inflammation [1,2]. Genetic models, such as KO mouse models, are valuable tools to study its function.

In IL-10-deficient conditions, genetic deletion of Cers2 limits the exacerbated inflammatory gene expression, suggesting that VLC ceramides synthesized by Cers2 are critical for heightened inflammation in this context [1]. In a CRISPR knock-in mouse model of the rs267738 variant in Cers2, homozygous mice had reduced liver Cers2 activity, enhanced diet-induced glucose intolerance, and hepatic steatosis, indicating that this SNP leads to a partial loss-of-function of Cers2, worsening metabolic parameters [2]. Also, CerS2 haploinsufficiency in mice conferred susceptibility to diet-induced steatohepatitis and insulin resistance, likely due to impaired β-oxidation [3].

In conclusion, Cers2 is essential in sphingolipid metabolism, particularly in the synthesis of VLC ceramides. Studies using KO/CKO mouse models have revealed its significance in inflammation, metabolic diseases like glucose intolerance, hepatic steatosis, steatohepatitis, and insulin resistance. Understanding Cers2 function through these models provides insights into the underlying mechanisms of these disease conditions and may offer potential therapeutic targets.