Sesn2-flox Mouse

Sesn2, also known as Sestrin2, is a powerful anti-oxidant. It is a stress-inducible protein that can be transcriptionally activated by factors like metabolic derangements, reactive oxygen species (ROS), and DNA-damage. One of its well-known functions is the inhibition of the mechanistic target of rapamycin complex 1 kinase (mTORC1), which is crucial for cell growth and autophagy regulation. It also plays a role in controlling ROS accumulation, metabolism, and cell viability [3].

In various disease models, Sesn2 shows distinct functions. In obese mice exposed to adriamycin, obesity decreased Sesn2 expression in the heart, predisposing to cardiotoxicity. Overexpression of Sesn2 blocked the destructive cascades and oxidative damage induced by high-fat diet/sodium palmitate combined with adriamycin, suggesting it could be a therapeutic target for anthracycline-related cardiotoxicity in obesity [1]. In sepsis models, Sesn2-deficient mice displayed defective mitophagy, leading to hyperactivation of inflammasomes and increased mortality, as Sesn2 suppresses NLRP3 inflammasome activation by inducing mitophagy in macrophages [2]. In denervated muscle atrophy models, knockdown of Sesn2 in the gastrocnemius aggravated atrophy, while Sesn2 was shown to protect against atrophy through the unfolded protein response and mitophagy [4].

In conclusion, Sesn2 has essential functions in regulating oxidative stress, autophagy, and cell survival. Gene-knockout (KO) mouse models in areas such as cardiovascular disease, sepsis, and muscle atrophy have revealed its protective roles. Understanding Sesn2's functions through these models provides potential therapeutic targets for stress-related diseases, highlighting its importance in disease prevention and treatment.