| First Author | Sladky VC | Year | 2025 |
| Journal | Sci Adv | Volume | 11 |
| Issue | 9 | Pages | eadq2339 |
| PubMed ID | 40020058 | Mgi Jnum | J:364098 |
| Mgi Id | MGI:7869038 | Doi | 10.1126/sciadv.adq2339 |
| Citation | Sladky VC, et al. (2025) Rapid and sustained degradation of the essential centrosome protein CEP192 in live mice using the AID2 system. Sci Adv 11(9):eadq2339 |
| abstractText | 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 gamma-tubulin recruitment to centrosomes impairing mitotic spindle assembly. Sustained CEP192 loss in vivo led to cell division failure and cell death in proliferative tissues. Thus, the second-generation AID system is well suited for rapid and/or sustained protein depletion in live mice to study essential functions in vivo. |
