Evidence map›Paper›PMID 33416493›Full record

ArticleeLife2021

A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes.

François Kroll, Gareth T Powell, Marcus Ghosh, Gaia Gestri, Paride Antinucci, Timothy J Hearn, Hande Tunbak, Sumi Lim, Harvey W Dennis, Joseph M Fernandez and 5 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
210citing papers in PubMed, 2 pooled it
16.6field-weighted citation impact, top 1% 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

210 citing papers in PubMed, 2 syntheses or guidelines pooled it, 340 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Advances in Fish Gene Editing.Animals : an open access journal from MDPI · 2026
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

150 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

François KrollDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.ORCID https://orcid.org/0000-0001-9908-2648
Gareth T PowellDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.
Marcus GhoshDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-2428-4605
Gaia GestriDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0001-8854-1546
Paride AntinucciDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0003-0573-5383
Timothy J HearnDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.
Hande TunbakWolfson Institute for Biomedical Research, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0003-3180-1401
Sumi LimDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.
Harvey W DennisSchool of Biological Sciences, Faculty of Science, University of Bristol, Bristol, United Kingdom.
Joseph M FernandezChild Study Center, Yale School of Medicine, New Haven, United States.
David WhitmoreDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.
Elena DreostiWolfson Institute for Biomedical Research, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-6738-7057
Stephen W WilsonDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-8557-5940
Ellen J HoffmanChild Study Center, Yale School of Medicine, New Haven, United States.
Jason RihelDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.ORCID https://orcid.org/0000-0003-4067-2066
University College London · GBWolfson Foundation · GBYale University · USUniversity of Bristol · GB

Funding

Biotechnology and Biological Sciences Research Council BB/T001844/1Medical Research Council G0501487Medical Research Council G0900994Medical Research Council MR/L003775/1Medical Research Council MR/T020164/1Wellcome TrustWellcome Trust 095722/Z/11/ZWellcome Trust 204708/Z/16/ZWellcome Trust 217150/Z/19/Z
6 · The paper itself

Abstract

Hundreds of human genes are associated with neurological diseases, but translation into tractable biological mechanisms is lagging. Larval zebrafish are an attractive model to investigate genetic contributions to neurological diseases. However, current CRISPR-Cas9 methods are difficult to apply to large genetic screens studying behavioural phenotypes. To facilitate rapid genetic screening, we developed a simple sequencing-free tool to validate gRNAs and a highly effective CRISPR-Cas9 method capable of converting >90% of injected embryos directly into F0 biallelic knockouts. We demonstrate that F0 knockouts reliably recapitulate complex mutant phenotypes, such as altered molecular rhythms of the circadian clock, escape responses to irritants, and multi-parameter day-night locomotor behaviours. The technique is sufficiently robust to knockout multiple genes in the same animal, for example to create the transparent triple knockout

Indexed as

CRISPR-Cas SystemsGene Knockout TechniquesAnimalsBehavior, AnimalEmbryo, NonmammalianGenetic TestingPhenotypeRNA, Guide, CRISPR-Cas SystemsZebrafishRNA, Guide, CRISPR-Cas Systemsbehaviourcircadian rhythmCRISPRG0geneticsgenomicsknockoutneurosciencesleepzebrafish

Identifiers

PMID33416493
PMCPMC7793621
OpenAlexW3120305566

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.