Evidence map›Paper›PMID 39349521›Full record

ArticleScientific reports2024

Impact of essential genes on the success of genome editing experiments generating 3313 new genetically engineered mouse lines.

Hillary Elrick, Kevin A Peterson, Brandon J Willis, Denise G Lanza, Elif F Acar, Edward J Ryder, Lydia Teboul, Petr Kasparek, Marie-Christine Birling, David J Adams and 31 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Review
  2. Article
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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

41 authors.

Hillary Elrick *The Centre for Phenogenomics, Toronto, ON, M5T 3H7, Canada.
Kevin A Peterson *The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Brandon J WillisMouse Biology Program, University of California-Davis, Davis, CA, 95618, USA.
Denise G LanzaDepartment of Molecular and Human Genetic, Baylor College of Medicine, Houston, TX, 77030, USA.
Elif F AcarThe Centre for Phenogenomics, Toronto, ON, M5T 3H7, Canada.
Edward J RyderWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Lydia TeboulThe Mary Lyon Centre, MRC Harwell Institute, Harwell Campus, Didcot, Oxon, OX11 0RD, UK.
Petr KasparekCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
Marie-Christine BirlingCNRS, INSERM, CELPHEDIA, PHENOMIN, Institut Clinique de la Souris, Université de Strasbourg, Illkirch-Graffenstaden, France.
David J AdamsWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Allan BradleyWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Robert E BraunThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Steve D BrownMRC Harwell Institute, Harwell, OX11 0RD, UK.
Adam CaulderThe Mary Lyon Centre, MRC Harwell Institute, Harwell Campus, Didcot, Oxon, OX11 0RD, UK.
Gemma F CodnerThe Mary Lyon Centre, MRC Harwell Institute, Harwell Campus, Didcot, Oxon, OX11 0RD, UK.
Francesco J DeMayoDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Mary E DickinsonDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, 77030, USA.
Brendan DoeWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Graham DuddyWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Marina GertsensteinThe Centre for Phenogenomics, Toronto, ON, M5T 3H7, Canada.
Leslie O GoodwinThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Yann HéraultCNRS, INSERM, CELPHEDIA, PHENOMIN, Institut Clinique de la Souris, Université de Strasbourg, Illkirch-Graffenstaden, France.
Lauri G LintottThe Centre for Phenogenomics, Toronto, ON, M5T 3H7, Canada.
K C Kent LloydMouse Biology Program, University of California-Davis, Davis, CA, 95618, USA.
Isabel LorenzoDepartment of Molecular and Human Genetic, Baylor College of Medicine, Houston, TX, 77030, USA.
Matthew MackenzieThe Mary Lyon Centre, MRC Harwell Institute, Harwell Campus, Didcot, Oxon, OX11 0RD, UK.
Ann-Marie MallonMRC Harwell Institute, Harwell, OX11 0RD, UK.
Colin McKerlieThe Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Helen ParkinsonEuropean Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK.
Ramiro Ramirez-SolisWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
John R SeavittThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Radislav SedlacekCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
William C SkarnesWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Damien SmedleyWilliam Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
Sara WellsThe Mary Lyon Centre, MRC Harwell Institute, Harwell Campus, Didcot, Oxon, OX11 0RD, UK.
Jacqueline K WhiteThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Joshua A WoodThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
International Mouse Phenotyping Consortium
Stephen A MurrayThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Jason D HeaneyDepartment of Molecular and Human Genetic, Baylor College of Medicine, Houston, TX, 77030, USA.
Lauryl M J NutterThe Centre for Phenogenomics, Toronto, ON, M5T 3H7, Canada. lauryl.nutter@sickkids.ca.

Funding

UM1HG006348: Cas9 Genome Integrity Supplemental ProposalUM1HG006348 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI Jason D. Heaney, Chih-Wei Logan Hsu · 2016 to 2026
$47.5M
The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)UM1OD023222 · OD · JACKSON LABORATORY · PI ROBERT E BRAUN, Stephen A Murray · 2016 to 2026
$47.2M
KOMP2-Phase3 Production and Phenotyping by the DTCC Consortium TCP Transfer to UC DavisUM1OD023221 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KC KENT LLOYD · 2016 to 2026
$45.7M
Mouse Phenotyping Informatics Infrastructure - MP12UM1HG006370 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Pilar Cacheiro Martinez, Helen Elizabeth Parkinson · 2016 to 2026
$20.4M
KOMP Phase II Mouse Production and CryopreservationU42OD011175 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2012 to 2015
$18.9M
High Throughput Production and Cryopreservation of Knockout MiceU42OD011185 · OD · JACKSON LABORATORY · PI MURRAY, STEPHEN A, TAFT, ROBERT A · 2012 to 2015
$17.9M
CRSPR II Supplement: Consortium for the production and cryopreservation of knockout miceU42OD011174 · OD · BAYLOR COLLEGE OF MEDICINE · PI BEAUDET, ARTHUR L. · 2012 to 2015
$17.7M
Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences RVO 68378050Genome Canada OGI-051Genome Canada OGI-090Genome Canada OGI-137Institut National de la Santé et de la Recherche Médicale ANR-10-IDEX-0002-02Institut National de la Santé et de la Recherche Médicale ANR-10-INBS-07Institut National de la Santé et de la Recherche Médicale ANR-10-LABX-0030-INRTMedical Research Council MC_UP_1502/3Ministry of Education, Youth and Sports of the Czech Republic LM2018126NHGRI NIH HHS UM1 HG006370NIH HHS U42 OD011174NIH HHS U42OD011174NIH HHS U42 OD011175NIH HHS U42OD011175NIH HHS U42 OD011185NIH HHS U42OD011185NIH HHS UM1HG006370NIH HHS UM1 OD023221NIH HHS UM1OD023221NIH HHS UM1 OD023222NIH HHS UM1OD023222NIH HHS UMIHG006348Ontario Genomics OGI-051Ontario Genomics OGI-090Ontario Genomics OGI-137Wellcome Trust
6 · The paper itself

Abstract

The International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affecting in vivo gene engineering with Cas9. Mouse line production has two critical steps - generation of founders with the desired allele and germline transmission (GLT) of that allele from founders to offspring. A systematic evaluation of the variables impacting success rates identified gene essentiality as the primary factor influencing successful production of null alleles. Collectively, our findings provide best practice recommendations for using Cas9 to generate alleles in mouse essential genes, many of which are orthologs of genes linked to human disease.

Indexed as

Gene EditingGenes, EssentialMice, KnockoutAllelesAnimalsCRISPR-Cas SystemsFemaleGenetic EngineeringMaleMiceMice, Inbred C57BLPhenotypeCas9Genome editingKnockoutMouse

Identifiers

PMID39349521
PMCPMC11443006

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Registered trials

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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.