Rapid and sustained degradation of the essential centrosome protein CEP192 in live mice using the AID2 system.

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 auxin-inducible degron (AID) system is a powerful tool for analyzing inducible protein loss in vitro, but it is toxic to mice. 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-phenyl-indole-3-acetic acid is well tolerated over 2 weeks and drives near-complete CEP192 degradation in less than 1 hour in vivo. CEP192 loss did not affect centriole duplication but decreased γ-tubulin recruitment to centrosomes impairing mitotic spindle assembly. Sustained CEP192 loss in vivo l

SUBMITTER: Sladky VC 

PROVIDER: S-EPMC11870075 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature