Wdr24-flox Mouse

Wdr24 is an essential component of the GATOR2 complex. The GATOR2 complex is key in linking amino acid signals to the mTORC1 pathway, which is a central regulator of metabolism and cell growth [1,2,3,4,5,6,7,8,9,10]. By being part of GATOR2, Wdr24 is involved in processes like nutrient sensing, and its function is crucial for normal cell growth and metabolism. Genetic models, such as mouse models, have been valuable in studying Wdr24's functions.

In phosphomimetic Wdr24S155D knock-in mice, there is early embryonic lethality and reduced mTORC1 activity, while phospho-deficient Wdr24S155A knock-in mice are more resistant to fasting and display elevated mTORC1 activity. This shows that AMPK-mediated phosphorylation of Wdr24 at S155 modulates glucose-induced mTORC1 activation [2]. In addition, Wdr24 ablation in mice leads to severe growth defects and embryonic lethality at E10.5, indicating that Wdr24 is essential for transmitting amino acid availability to mTORC1 during embryonic development [4].

In conclusion, Wdr24, as a part of the GATOR2 complex, is vital for regulating mTORC1 activity in response to nutrient signals such as amino acids and glucose. The study of Wdr24 using gene knockout mouse models has revealed its significance in embryonic development and metabolism-related processes. These findings have implications for understanding diseases where mTORC1 signaling is aberrantly activated, like certain cancers [1,2,4,8,9].