Evidence map›Paper›PMID 30511203›Full record

ArticleTranslational stroke research2019

Induction of Brain Arteriovenous Malformation Through CRISPR/Cas9-Mediated Somatic Alk1 Gene Mutations in Adult Mice.

Wan Zhu, Daniel Saw, Miriam Weiss, Zhengda Sun, Meng Wei, Sonali Shaligram, Sen Wang, Hua Su

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational stroke research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
1.2field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.

  1. Translational relevance of animal models available on brain arteriovenous malformations, a systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Pooled it
  2. Pooled it
  3. Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Genome Editing with AAV-BR1-CRISPR in Postnatal Mouse Brain Endothelial Cells.International journal of biological sciences · 2022
    Article
  10. Review
  11. Recent Advances in Basic Research for Brain Arteriovenous Malformation.International journal of molecular sciences · 2019
    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.

Wan ZhuCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Daniel SawCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Miriam WeissCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Zhengda SunDepartment of Radiology, University of California, San Francisco, San Francisco, CA, USA.
Meng WeiCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Sonali ShaligramCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Sen WangCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Hua SuCenter for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA. hua.su@ucsf.edu.ORCID 0000-0003-1566-9877
University of California, San Francisco · US

Funding

Uncover the Pathogenesis of Brain Arteriovenous MalformationR01NS027713 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SU, HUA · 1990 to 2023
$8.6M
Cell type-specific influences on HHT pathogenesisR01HL122774 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SU, HUA · 2015 to 2018
$1.6M
NHLBI NIH HHS R01 HL122774NINDS NIH HHS R01 NS027713
6 · The paper itself

Abstract

Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. The pathogenesis of bAVM has not been fully understood. Animal models are important tools for dissecting bAVM pathogenesis and testing new therapies. We have developed several mouse bAVM models using genetically modified mice. However, due to the body size, mouse bAVM models have some limitations. Recent studies identified somatic mutations in sporadic human bAVM. To develop a feasible tool to create sporadic bAVM in rodent and animals larger than rodent, we made tests using the CRISPR/Cas9 technique to induce somatic gene mutations in mouse brain in situ. Two sequence-specific guide RNAs (sgRNAs) targeting mouse Alk1 exons 4 and 5 were cloned into pAd-Alk1e4sgRNA + e5sgRNA-Cas9 plasmid. These sgRNAs were capable to generate mutations in Alk1 gene in mouse cell lines. After packaged into adenovirus, Ad-Alk1e4sgRNA + e5sgRNA-Cas9 was co-injected with an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF) into the brains of wild-type C57BL/6J mice. Eight weeks after viral injection, bAVMs were detected in 10 of 12 mice. Compared to the control (Ad-GFP/AAV-VEGF-injected) brain, 13% of Alk1 alleles were mutated and Alk1 expression was reduced by 26% in the Ad-Alk1e4sgRNA + e5sgRNA-Cas9/AAV-VEGF-injected brains. Around the Ad-Alk1e4sgRNA + e5sgRNA-Cas9/AAV-VEGF injected site, Alk1-null endothelial cells were detected. Our data demonstrated that CRISPR/Cas9 is a feasible tool for generating bAVM model in animals.

Indexed as

Disease Models, AnimalActivin Receptors, Type IIAnimalsCRISPR-Cas SystemsEndothelial CellsFemaleGene ExpressionGenetic VectorsIntracranial Arteriovenous MalformationsMaleMice, Inbred C57BLMutationActivin Receptors, Type IIAcvrl1 protein, mouseAlk1Brain arteriovenous malformationCRISPR/Cas9Somatic gene mutation

Identifiers

PMID30511203
PMCPMC6546562
OpenAlexW2902274037

What OpenQuestion holds

Textmetadata
LicenceTDM
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.