Nudt3-flox Mouse

Nudt3, a member of the NUDIX family, has multiple essential functions. It acts as an mRNA decapping enzyme, playing a role in the highly regulated mRNA decay process, and is also involved in polyphosphate (polyP) degradation. In mammals, polyP is crucial for physiological processes like coagulation, inflammation, and stress response, and Nudt3-Zn2+ mediates the oxidative stress response through polyP degradation [1]. Additionally, Nudt3 is associated with pathways related to cell migration, insulin signaling, and fat metabolism, highlighting its overall biological importance. Genetic models such as Drosophila and mice have been used to study its functions [2,3].

Knocking down the Drosophila Nudt3 homolog Aps in the nervous system or insulin-producing cells leads to hyperinsulinemia-like phenotypes, including decreased circulating trehalose and carbohydrate levels under starvation, as well as reduced lipid recruitment during starvation, hyperphagia, and decreased expression of genes inhibited by insulin signaling [3]. In mice, Nudt3 mRNA and protein are abundantly expressed in the brain, especially in reward-and feeding-related regions, and its mRNA expression is up-regulated in the hypothalamus and brainstem of food-deprived mice [3]. In pigs, knockdown of Nudt3 reduces the percentage of EdU+ cells and expression of cell cycle repressors, while increasing lipid droplets in adipocytes, and exogenous expression in adipose tissue reduces high-fat diet-induced fat expansion in mice. Also, rs694899689 was identified as a potential genetic variant modulating Nudt3 expression and backfat thickness in pigs [4].

In conclusion, Nudt3 is involved in diverse biological processes such as oxidative stress response, mRNA regulation, cell migration, insulin signaling, and fat metabolism. Studies using genetic models like Drosophila and mice have revealed its roles in disease-related conditions such as obesity-related metabolic disorders and adipogenesis in pigs, providing insights into the underlying molecular mechanisms and potential therapeutic targets.