Mast3-flox Mouse

MAST3, short for microtubule-associated serine/threonine-protein kinase 3, is involved in multiple biological processes. It plays a role in intracellular signal transduction, peptidyl-serine phosphorylation, and cytoskeleton organization [2]. In the immune system, it modulates the inflammatory response, for example, in Inflammatory Bowel Disease (IBD) by influencing the NF-κB activity and in rheumatoid arthritis (RA) by regulating the proliferation and inflammatory response of fibroblast-like synoviocytes [2,3,4]. In the nervous system, it has a distinct expression pattern in the developing and mature brain, and is potentially associated with neurological diseases [1,5].

In individuals with epilepsy, de novo missense variants in the STK domain of MAST3 were identified. In vitro analysis of HEK293T cells transfected with MAST3 cDNA carrying patient-specific missense variants showed variable but generally lower expression, with increased phosphorylation of the target ARPP-16, suggesting a gain-of-function mechanism [1]. In zebrafish, abnormal morphology of the central nervous system was observed in mast3a/b crispants, indicating its role in neurodevelopmental diseases [5].

In conclusion, MAST3 is a key gene involved in regulating immune responses in IBD and RA, and is also associated with epilepsy and neurodevelopmental diseases. The use of in vitro cell models and in vivo zebrafish models has provided insights into its function in disease-related biological processes, highlighting its importance in understanding the pathogenesis of these diseases [1,2,3,4,5].