The AID2 system offers a potent tool for rapid, reversible, or sustained degradation of essential proteins in live mice.

ABSTRACT: Studying essential genes required for dynamic processes in live mice is challenging as genetic perturbations are irreversible and limited by slow protein depletion kinetics. The first-generation auxin-inducible-degron (AID) system is a powerful tool for analyzing inducible protein loss in cultured cells. However, auxin administration is toxic to mice, preventing its long-term use in animals. Here, we use an optimized second-generation AID system to achieve the conditional and reversible loss of the essential centrosomal protein CEP192 in live mice. We show that the auxin derivative 5-Ph-IAA is well tolerated over two weeks and drives near-complete CEP192-mAID degradation in less than one hour in vivo. Prolonged CEP192 loss led to cell division failure and cell death in proliferative

SUBMITTER: Sladky VC 

PROVIDER: S-EPMC11185741 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature