Evidence map›Paper›PMID 31877124›Full record

ArticlePLoS genetics2019

CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4.

Andrew M Garrett, Peter J Bosch, David M Steffen, Leah C Fuller, Charles G Marcucci, Alexis A Koch, Preeti Bais, Joshua A Weiner, Robert W Burgess

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

34 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
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  11. Complex Regulation of Protocadherin Epigenetics on Aging-Related Brain Health.medRxiv : the preprint server for health sciences · 2024
    Article
  12. Article
  13. The clustered gamma protocadherin PcdhγC4 isoform regulates cortical interneuron programmed cell death in the mouse cortex.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  14. The Role of Protocadherin γ in Adult Sensory Neurons and Skin Reinnervation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  15. Visualization ofiScience · 2023
    Article
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  18. Review
  19. A Unique Role for Protocadherin γC3 in Promoting Dendrite Arborization through an Axin1-Dependent Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    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

9 authors at 3 institutions in 1 country.

Andrew M GarrettDepartment of Pharmacology and Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University, Detroit, Michigan, United States of America.ORCID 0000-0001-5765-2585
Peter J BoschDepartment of Biology and Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, United States of America.ORCID 0000-0002-0480-3439
David M SteffenDepartment of Biology and Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, United States of America.
Leah C FullerDepartment of Biology and Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, United States of America.
Charles G MarcucciDepartment of Biology and Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, United States of America.ORCID 0000-0001-9900-5431
Alexis A KochDepartment of Pharmacology and Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University, Detroit, Michigan, United States of America.ORCID 0000-0003-3388-8555
Preeti BaisThe Jackson Laboratory, Bar Harbor, Maine, United States of America.
Joshua A WeinerDepartment of Biology and Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, United States of America.ORCID 0000-0002-3352-2847
Robert W BurgessThe Jackson Laboratory, Bar Harbor, Maine, United States of America.ORCID 0000-0002-9229-3407
University of Iowa · USJackson Laboratory · USWayne State University · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
Elucidating Functions of the Gamma-Protocadherins in CNS Synapse DevelopmentR01NS055272 · NINDS · UNIVERSITY OF IOWA · PI WEINER, JOSHUA A · 2007 to 2020
$5.1M
Reducing Diversity at the Gamma Protocadherin Locus by CRISPR TargetingR21NS090030 · NINDS · JACKSON LABORATORY · PI BURGESS, ROBERT W., WEINER, JOSHUA A · 2014 to 2015
$506k
Elucidating Functions of the Gamma-Protocadherins in CNS DevelopmentR56NS055272 · NINDS · UNIVERSITY OF IOWA · PI WEINER, JOSHUA A · 2012 to 2012
$432k
NCI NIH HHS P30 CA034196NINDS NIH HHS R01 NS055272NINDS NIH HHS R21 NS090030NINDS NIH HHS R56 NS055272
6 · The paper itself

Abstract

The mammalian Pcdhg gene cluster encodes a family of 22 cell adhesion molecules, the gamma-Protocadherins (γ-Pcdhs), critical for neuronal survival and neural circuit formation. The extent to which isoform diversity-a γ-Pcdh hallmark-is required for their functions remains unclear. We used a CRISPR/Cas9 approach to reduce isoform diversity, targeting each Pcdhg variable exon with pooled sgRNAs to generate an allelic series of 26 mouse lines with 1 to 21 isoforms disrupted via discrete indels at guide sites and/or larger deletions/rearrangements. Analysis of 5 mutant lines indicates that postnatal viability and neuronal survival do not require isoform diversity. Surprisingly, given reports that it might not independently engage in trans-interactions, we find that γC4, encoded by Pcdhgc4, is the only critical isoform. Because the human orthologue is the only PCDHG gene constrained in humans, our results indicate a conserved γC4 function that likely involves distinct molecular mechanisms.

Indexed as

Alternative SplicingMutationAnimalsCadherin Related ProteinsCadherinsCRISPR-Cas SystemsEmbryonic DevelopmentExonsFemaleHumansINDEL MutationMaleMiceMultigene FamilyNeuronsProtein IsoformsCadherin Related ProteinsCadherinsGamma-protocadherinsProtein Isoforms

Identifiers

PMID31877124
PMCPMC6957209
OpenAlexW2998564716

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.