Evidence map›Paper›PMID 19109564›Full record

ArticleBlood2009

Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins.

Marie N O'Connor, Isabelle I Salles, Ana Cvejic, Nicholas A Watkins, Adam Walker, Stephen F Garner, Chris I Jones, Iain C Macaulay, Michael Steward, Jaap-Jan Zwaginga and 8 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  11. Defective fibrin deposition and thrombus stability in BambiJournal of thrombosis and haemostasis : JTH · 2019
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  15. Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
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  18. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 10 institutions in 3 countries.

Marie N O'ConnorDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.
Isabelle I Salles
Ana Cvejic
Nicholas A Watkins
Adam Walker
Stephen F Garner
Chris I Jones
Iain C Macaulay
Michael Steward
Jaap-Jan Zwaginga
Sarah L Bray
Frank Dudbridge
Bernard de Bono
Alison H Goodall
Hans Deckmyn
Derek L Stemple
Willem H Ouwehand
Bloodomics Consortium
National Health Service · GBUniversity of Cambridge · GBUniversity of Leicester · GBKU Leuven · BELeiden University Medical Center · NLMedical Research Council · GBMRC Biostatistics Unit · GBResearch Institute for Chromatography · BEWellcome Sanger Institute · GBWellcome Trust · GB

Funding

Wellcome TrustWellcome Trust WT077037/Z/05/ZWellcome Trust WT082597/Z/07/Z
6 · The paper itself

Abstract

In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)-based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.

Indexed as

GenomicsAnimalsBlood PlateletsBlotting, WesternEmbryo, NonmammalianGene Expression ProfilingHumansLasersMembrane ProteinsOligonucleotide Array Sequence AnalysisOligonucleotides, AntisensePhenotypePlatelet AggregationThrombosisZebrafishZebrafish ProteinsMembrane ProteinsOligonucleotides, AntisenseZebrafish Proteins

Identifiers

PMID19109564
PMCPMC2680375
OpenAlexW2069604153

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.