Evidence map›Paper›PMID 27161796›Full record

ArticleScientific reports2016

A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.

Michael R Williams, Catherine J Fricano-Kugler, Stephanie A Getz, Patrick D Skelton, Jeonghoon Lee, Christian P Rizzuto, Joseph S Geller, Meijie Li, Bryan W Luikart

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 43 citations in OpenAlex.

  1. PTEN Subcellular Localization Dictates Function.bioRxiv : the preprint server for biology · 2026
    Article
  2. Genes & diseases · 2025
    Review
  3. Pathogenic variants in autism geneProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. Article
  5. Article
  6. Knockout ofInternational journal of molecular sciences · 2022
    Article
  7. PTEN Regulates Dendritic Arborization by Decreasing Microtubule Polymerization Rate.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  8. Review
  9. Understanding the Potential of Genome Editing in Parkinson's Disease.International journal of molecular sciences · 2021
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. The Role of PTEN in Neurodevelopment.Molecular neuropsychiatry · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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 1 institution in 1 country.

Michael R WilliamsDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Catherine J Fricano-KuglerDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Stephanie A GetzDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Patrick D SkeltonDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Jeonghoon LeeDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Christian P RizzutoDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Joseph S GellerDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Meijie LiDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Bryan W LuikartDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
Dartmouth College · US

Funding

The Impact of PTEN Signaling on Neuronal Form and FunctionR01MH097949 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BRYAN W LUIKART · 2012 to 2026
$7.4M
NIMH NIH HHS R01 MH097949
6 · The paper itself

Abstract

Retroviruses expressing a fluorescent protein, Cas9, and a small guide RNA are used to mimic nonsense PTEN mutations from autism patients in developing mouse neurons. We compare the cellular phenotype elicited by CRISPR-Cas9 to those elicited using shRNA or Cre/Lox technologies and find that knockdown or knockout (KO) produced a corresponding moderate or severe neuronal hypertrophy in all cells. In contrast, the Cas9 approach produced missense and nonsense Pten mutations, resulting in a mix of KO-equivalent hypertrophic and wild type-like phenotypes. Importantly, despite this mixed phenotype, the neuronal hypertrophy resulting from Pten loss was evident on average in the population of manipulated cells. Having reproduced the known Pten KO phenotype using the CRISPR-Cas9 system we design viruses to target a gene that has recently been associated with autism, KATNAL2. Katnal2 deletion in the mouse results in decreased dendritic arborization of developing neurons. We conclude that retroviral implementation of the CRISPR-Cas9 system is an efficient system for cellular phenotype discovery in wild-type animals.

Indexed as

CRISPR-Cas SystemsAnimalsAutistic DisorderCell EnlargementFemaleGene EditingHumansKataninMaleMice, Inbred C57BLMutationNeuronsPhenotypePTEN PhosphohydrolaseRetroviridaeRNA InterferenceKataninKATNAL2 protein, mousePTEN Phosphohydrolase

Identifiers

PMID27161796
PMCPMC4861960
OpenAlexW2417922500

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.