Evidence map›Paper›PMID 27385011›Full record

ArticleDevelopment (Cambridge, England)2016

Leapfrogging: primordial germ cell transplantation permits recovery of CRISPR/Cas9-induced mutations in essential genes.

Ira L Blitz, Margaret B Fish, Ken W Y Cho

Open access · greenAbstract read
In one paragraph

Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Advancing genetic and genomic technologies deepen the pool for discovery in Xenopus tropicalis.Developmental dynamics : an official publication of the American Association of Anatomists · 2019
    Review
  6. Modeling congenital kidney diseases inDisease models & mechanisms · 2019
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Naming CRISPR alleles: endonuclease-mediated mutation nomenclature across species.Mammalian genome : official journal of the International Mammalian Genome Society · 2017
    Review
  12. Article
  13. A frog's view of EphrinB signaling.Genesis (New York, N.Y. : 2000) · 2017
    Review
  14. Review
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

3 authors at 1 institution in 1 country.

Ira L Blitz4410 Natural Sciences Building 2, Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA ilblitz@uci.edu.ORCID 0000-0002-0173-3287
Margaret B Fish4410 Natural Sciences Building 2, Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
Ken W Y Cho4410 Natural Sciences Building 2, Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
University of California, Irvine · US

Funding

Deciphering the gene regulatory network controlling vertebrate endodermal fatesR01HD073179 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI CHO, KEN W.Y., MJOLSNESS, ERIC D · 2013 to 2017
$2.9M
Genome engineering in Xenopus using the CRISPR/Cas systemR21HD080684 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLITZ, IRA L · 2014 to 2015
$419k
NICHD NIH HHS R01 HD073179NICHD NIH HHS R21 HD080684
6 · The paper itself

Abstract

CRISPR/Cas9 genome editing is revolutionizing genetic loss-of-function analysis but technical limitations remain that slow progress when creating mutant lines. First, in conventional genetic breeding schemes, mosaic founder animals carrying mutant alleles are outcrossed to produce F1 heterozygotes. Phenotypic analysis occurs in the F2 generation following F1 intercrosses. Thus, mutant analyses will require multi-generational studies. Second, when targeting essential genes, efficient mutagenesis of founders is often lethal, preventing the acquisition of mature animals. Reducing mutagenesis levels may improve founder survival, but results in lower, more variable rates of germline transmission. Therefore, an efficient approach to study lethal mutations would be useful. To overcome these shortfalls, we introduce 'leapfrogging', a method combining efficient CRISPR mutagenesis with transplantation of mutated primordial germ cells into a wild-type host. Tested using Xenopus tropicalis, we show that founders containing transplants transmit mutant alleles with high efficiency. F1 offspring from intercrosses between F0 animals that carry embryonic lethal alleles recapitulate loss-of-function phenotypes, circumventing an entire generation of breeding. We anticipate that leapfrogging will be transferable to other species.

Indexed as

AnimalsAnuraBlastulaCRISPR-Cas SystemsEmbryo, NonmammalianFemaleGerm CellsMaleMutagenesisMutationTranscription Activator-Like Effector NucleasesXenopusTranscription Activator-Like Effector NucleasesCRISPR/Cas9Genome editingKnockoutsPrimordial germ cellsTALENsXenopus

Identifiers

PMID27385011
PMCPMC5004912
OpenAlexW2470153803

What OpenQuestion holds

Textmetadata
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.