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Abstract / Description of output
Auxin-inducible degrons are a chemical genetic tool for targeted protein degradation and are widely used to study protein function in cultured mammalian cells. Here, we develop CRISPR-engineered mouse lines that enable rapid and highly specific degradation of tagged endogenous proteins in vivo. Most but not all cell types are competent for degradation. By combining ligand titrations with genetic crosses to generate animals with different allelic combinations, we show that degradation kinetics depend upon the dose of the tagged protein, ligand, and the E3 ligase substrate receptor TIR1. Rapid degradation of condensin I and II - two essential regulators of mitotic chromosome structure - revealed that both complexes are individually required for cell division in precursor lymphocytes, but not in their differentiated peripheral lymphocyte derivatives. This generalisable approach provides unprecedented temporal control over the dose of endogenous proteins in mouse models, with implications for studying essential biological pathways and modelling drug activity in mammalian tissues.
Keywords / Materials (for Non-textual outputs)
- Indoleacetic Acids/metabolism
- Ubiquitin-Protein Ligases/metabolism
FingerprintDive into the research topics of 'Rapid and specific degradation of endogenous proteins in mouse models using auxin-inducible degrons'. Together they form a unique fingerprint.
- 1 Finished
1/02/14 → 31/01/19
- 1 Preprint
Wood, A. J., MacDonald, L. & Taylor, G., 13 Jan 2022, bioRxiv, at Cold Spring Harbor Laboratory.
Research output: Working paper › Preprint
Martha Koerner (Manager)Bioresearch and Veterinary Services
Alex Von Kriegsheim (Manager)Deanery of Molecular, Genetic and Population Health Sciences