Cers1-flox Mouse

Cers1, short for ceramide synthase 1, is a key enzyme in the de novo sphingolipid synthesis pathway. It is responsible for generating C18:0 ceramide, a central molecule in sphingolipid metabolism that has important functions in membrane structure and cellular signaling. Alterations in Cers1-related processes can impact various biological pathways, making it biologically significant [1,2,3,4]. Genetic models, such as knockout (KO) mouse models, have been crucial in studying Cers1's function.

In KO mouse models, global or skeletal-muscle-specific knockout of CerS1 (CerS1ΔSkM) leads to reduced muscle C18:0 ceramide content, accompanied by improvements in systemic glucose homeostasis. This indicates that CerS1-derived C18:0 ceramide in skeletal muscle promotes obesity-induced insulin resistance [3]. In aged mice, pharmacological or genetic inhibition of CERS1 exacerbates age-related skeletal muscle impairment, including blunted myogenesis and deteriorated muscle mass and function, associated with inflammation and fibrosis [2].

In summary, Cers1 is essential for regulating the production of C18:0 ceramide, which is involved in multiple biological processes. KO mouse models have revealed its role in obesity-related insulin resistance and age-related muscle dysfunction, highlighting its importance in understanding these disease areas.