Evidence map›Paper›PMID 35736539›Full record

ArticleeLife2022

Rapid and specific degradation of endogenous proteins in mouse models using auxin-inducible degrons.

Lewis Macdonald, Gillian C Taylor, Jennifer Margaret Brisbane, Ersi Christodoulou, Lucy Scott, Alex von Kriegsheim, Janet Rossant, Bin Gu, Andrew J Wood

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 44 citations in OpenAlex.

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  5. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Lewis Macdonald *MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Gillian C Taylor *MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Jennifer Margaret BrisbaneMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0003-4943-5331
Ersi ChristodoulouMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Lucy ScottMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Alex von KriegsheimCancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-4952-8573
Janet RossantProgram in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada.ORCID 0000-0002-3731-5466
Bin GuDepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, United States.ORCID 0000-0002-5594-2463
Andrew J WoodMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-0653-2070
Institute of Genetics and Cancer · GBEdinburgh Cancer Research · GBHospital for Sick Children · CAMichigan State University · US

Funding

CIHR FDN-143334Medical Research Council MC_PC_21040Wellcome TrustWellcome Trust 102560/Z/13/Z
6 · The paper itself

Abstract

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.

Indexed as

Indoleacetic AcidsUbiquitin-Protein LigasesAnimalsChromosomesLigandsMammalsMiceProteolysisIndoleacetic AcidsLigandsUbiquitin-Protein Ligaseschromosomescondensindegrondevelopmental biologygene expressiongenetic toolsmouse

Identifiers

PMID35736539
PMCPMC9273210
OpenAlexW4283372167

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.