Selenow-flox Mouse

SELENOW, also known as selenoprotein W and SEPW1, is a selenocysteine-containing selenoprotein. It is involved in various biological processes and is part of the thioredoxin-like family of selenoproteins [5,7]. SELENOW plays a role in redox-related functions, and its expression and function are associated with multiple pathways and biological systems [7]. Genetic models, especially KO mouse models, have been crucial in understanding its functions.

In muscle-related studies, SELENOW KO in mouse models of dexamethasone-induced muscle atrophy and age-related sarcopenia aggravated muscle mass loss. Mechanistically, it suppressed the RAC1-mTOR cascade through interaction with RAC1, leading to an imbalance in protein synthesis and degradation [1].

In an Alzheimer's disease mouse model, SELENOW deficiency led to synaptic defects, tau dysregulation, and memory deficits, while overexpression ameliorated memory impairment and tau-related pathologies, as SELENOW promotes tau degradation through the ubiquitin-proteasome system [2].

In non-alcoholic fatty liver disease, loss of SelW alleviated hepatic steatosis induced by a high-fat diet, and SelW modulated the translocation of Pyruvate Kinase M2 into the nucleus, mediating mitochondrial apoptosis and related inflammatory responses [3].

In experimental colitis, Selenow KO mice showed exacerbated acute colitis, with loss of epithelial barrier integrity and decreased expression of key epithelial-related proteins, indicating Selenow's role in resolving inflammation and promoting intestinal epithelial repair [4].

In bone remodeling, SELENOW-deficient mice exhibited a high bone mass phenotype, as SELENOW regulates osteoclastogenic genes and its deficiency suppresses osteoclast formation [6].

In conclusion, SELENOW is essential in multiple biological processes such as muscle mass maintenance, tau homeostasis, liver lipid metabolism, intestinal epithelial repair, and bone remodeling. Studies using KO mouse models have revealed its significance in age-related sarcopenia, Alzheimer's disease, non-alcoholic fatty liver disease, experimental colitis, and osteoporosis, providing insights into potential therapeutic strategies for these diseases.