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The AID2 system offers a potent tool for rapid, reversible, or sustained degradation of essential proteins in live mice.
Sladky, Valentina C; Strong, Margaret A; Tapias-Gomez, Daniel; Jewett, Cayla E; Drown, Chelsea G; Scott, Phillip M; Holland, Andrew J.
Afiliación
  • Sladky VC; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 21205, MD, Baltimore, USA.
  • Strong MA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 21205, MD, Baltimore, USA.
  • Tapias-Gomez D; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 21205, MD, Baltimore, USA.
  • Jewett CE; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 21205, MD, Baltimore, USA.
  • Drown CG; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 21205, MD, Baltimore, USA.
  • Scott PM; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 21205, MD, Baltimore, USA.
  • Holland AJ; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 21205, MD, Baltimore, USA.
bioRxiv ; 2024 Jun 04.
Article en En | MEDLINE | ID: mdl-38895390
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 tissues. Thus, the second-generation AID system is well suited for rapid and/or sustained protein depletion in live mice, offering a valuable new tool for interrogating protein function in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos