Evidence map›Paper›PMID 22684503›Full record

ArticleNucleic acids research2012

Highly efficient generation of heritable zebrafish gene mutations using homo- and heterodimeric TALENs.

Lindsay Cade, Deepak Reyon, Woong Y Hwang, Shengdar Q Tsai, Samir Patel, Cyd Khayter, J Keith Joung, Jeffry D Sander, Randall T Peterson, Jing-Ruey Joanna Yeh

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
20.9field-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

124 citing papers in PubMed, 244 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Article
  6. Mechanistic toxicology in light of genetic compensation.Toxicological sciences : an official journal of the Society of Toxicology · 2024
    Article
  7. Review
  8. Scalable CRISPR Screens in Zebrafish Using MIC-Drop.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
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  16. Review
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  19. Review
  20. Article

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

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

10 authors at 2 institutions in 1 country.

Lindsay CadeCardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Deepak Reyon
Woong Y Hwang
Shengdar Q Tsai
Samir Patel
Cyd Khayter
J Keith Joung
Jeffry D Sander
Randall T Peterson
Jing-Ruey Joanna Yeh
Harvard University Press · USHarvard University · US

Funding

MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
ADVANCING ZINC FINGER NUCLEASES FOR TARGETED GENOME MANIPULATIONR01GM088040 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH, PETERSON, RANDALL T · 2009 to 2016
$4.5M
Advancing stem cell technologies using engineered zinc finger proteinsDP1GM105378 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2012 to 2014
$2.6M
Advancing stem cell technologies using engineered zinc finger proteinsDP1OD006862 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2010 to 2011
$1.8M
Discovering chemical tools for acute myelogenous leukemiaR01CA140188 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI YEH, JING-RUEY JOANNA · 2010 to 2014
$1.8M
Age factors, mutations, and chemical suppressors of acute myelogenous leukemiaK01AG031300 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI YEH, JING-RUEY JOANNA · 2008 to 2012
$662k
Improving the Efficiency of Gene Targeting Using TAL Effector NucleasesF32GM105189 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI TSAI, SHENGDAR · 2013 to 2014
$107k
NCI NIH HHS R01 CA140188NCI NIH HHS T32 CA009216NIA NIH HHS K01 AG031300NIGMS NIH HHS DP1 GM105378NIGMS NIH HHS F32 GM105189NIGMS NIH HHS R01 GM088040NIH HHS DP1 OD006862
6 · The paper itself

Abstract

Transcription activator-like effector nucleases (TALENs) are powerful new research tools that enable targeted gene disruption in a wide variety of model organisms. Recent work has shown that TALENs can induce mutations in endogenous zebrafish genes, but to date only four genes have been altered, and larger-scale tests of the success rate, mutation efficiencies and germline transmission rates have not been described. Here, we constructed homodimeric TALENs to 10 different targets in various endogenous zebrafish genes and found that 7 nuclease pairs induced targeted indel mutations with high efficiencies ranging from 2 to 76%. We also tested obligate heterodimeric TALENs and found that these nucleases induce mutations with comparable or higher frequencies and have better toxicity profiles than their homodimeric counterparts. Importantly, mutations induced by both homodimeric and heterodimeric TALENs are passed efficiently through the germline, in some cases reaching 100% transmission. For one target gene sequence, we observed substantially reduced mutagenesis efficiency for a variant site bearing two mismatched nucleotides, raising the possibility that TALENs might be used to perform allele-specific gene disruption. Our results suggest that construction of one to two heterodimeric TALEN pairs for any given gene will, in most cases, enable researchers to rapidly generate knockout zebrafish.

Indexed as

Gene Knockout TechniquesMutationAllelesAnimalsBase SequenceDeoxyribonucleases, Type II Site-SpecificDimerizationDNA-Binding ProteinsMolecular Sequence DataMutagenesisTrans-ActivatorsZebrafishDeoxyribonucleases, Type II Site-SpecificDNA-Binding Proteinsendodeoxyribonuclease FokITrans-Activators

Identifiers

PMID22684503
PMCPMC3439908
OpenAlexW2098248120

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.