Evidence map›Paper›PMID 34941868›Full record

ArticlePLoS biology2021

Meiotic Cas9 expression mediates gene conversion in the male and female mouse germline.

Alexander J Weitzel, Hannah A Grunwald, Ceri Weber, Rimma Levina, Valentino M Gantz, Stephen M Hedrick, Ethan Bier, Kimberly L Cooper

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Y-linked editors for invasive rodent control.Molecular biology and evolution · 2026
    Article
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  6. Review
  7. Article
  8. Engineering drive-selection balance for localized population suppression with neutral dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Gene drive-mediated population elimination for biodiversity conservation. When you come to a fork in the road, take it.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. Article
  18. Leveraging a natural murine meiotic drive to suppress invasive populations.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  19. Article
  20. 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

8 authors at 1 institution in 1 country.

Alexander J WeitzelDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0002-1713-158X
Hannah A GrunwaldDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0002-0553-906X
Ceri WeberDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0001-7846-2094
Rimma LevinaDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0001-7143-9174
Valentino M GantzDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0003-2453-0711
Stephen M HedrickDivision of Biological Sciences, Section of Molecular Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0002-6345-8751
Ethan BierDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0002-2892-3005
Kimberly L CooperDivision of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0001-5892-8838
University of California San Diego · US

Funding

GENETIC MECHANISMS AND REGULATIONT32GM007240 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 1985 to 2019
$23.8M
Pathways in Biological Sciences Training ProgramT32GM133351 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Matthew Daugherty, Randolph Y. Hampton · 2020 to 2026
$9.9M
Mutagenic chain reaction-facilitated immunotherapyR01AI131081 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BIER, ETHAN, GOLDRATH, ANANDA W · 2016 to 2020
$3.3M
Development of CRISPR-Cas9 gene drive technology in mice with potential for broad utility and applied geneticsR21GM129448 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COOPER, KIMBERLY LYNN · 2018 to 2019
$433k
NIAID NIH HHS R01 AI131081NIGMS NIH HHS R21 GM129448NIGMS NIH HHS T32 GM007240NIGMS NIH HHS T32 GM133351
6 · The paper itself

Abstract

Highly efficient gene conversion systems have the potential to facilitate the study of complex genetic traits using laboratory mice and, if implemented as a "gene drive," to limit loss of biodiversity and disease transmission caused by wild rodent populations. We previously showed that such a system of gene conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double-strand DNA break (DSB) is feasible in the female mouse germline. In the male germline, however, all DSBs were instead repaired by end joining (EJ) mechanisms to form an "insertion/deletion" (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homology-directed repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate gene conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient DSB formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of gene conversion and further increase the rate of "super-mendelian" inheritance from both male and female mice.

Indexed as

AnimalsCRISPR-Associated Protein 9CRISPR-Cas SystemsDNA Breaks, Double-StrandedDNA RepairFemaleGene ConversionGene EditingGene ExpressionGene Expression Regulation, DevelopmentalGenetic EngineeringGerm CellsMaleMeiosisMiceRecombinational DNA RepairCRISPR-Associated Protein 9RNA, Guide, CRISPR-Cas Systems

Identifiers

PMID34941868
PMCPMC8699911
OpenAlexW4200047645

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.