Evidence map›Paper›PMID 32132579›Full record

ArticleScientific reports2020

Disruption of the kringle 1 domain of prothrombin leads to late onset mortality in zebrafish.

Steven J Grzegorski, Zhilian Hu, Yang Liu, Xinge Yu, Allison C Ferguson, Hasam Madarati, Alexander P Friedmann, Deepak Reyon, Paul Y Kim, Colin A Kretz and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 21 citations in OpenAlex.

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  16. Fishing for answers to hemostatic and thrombotic disease: Genome editing in zebrafish.Research and practice in thrombosis and haemostasis · 2022
    Review
  17. Article
  18. Computational Integration of Renal Histology and Urinary Proteomics using Neural Networks.Proceedings of SPIE--the International Society for Optical Engineering
    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

12 authors at 6 institutions in 3 countries.

Steven J Grzegorski *Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Zhilian Hu *Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Yang LiuDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Xinge YuDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Allison C FergusonDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Hasam MadaratiDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Alexander P FriedmannDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Deepak ReyonMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
Paul Y KimDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Colin A KretzDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
J Keith JoungMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
Jordan A ShavitDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA. jshavit@umich.edu.
University of Michigan–Ann Arbor · USThrombosis and Atherosclerosis Research Institute · CAHarvard University · USMassachusetts General Hospital · USMcMaster University · CAMolecular Innovations (United States) · US

Funding

MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
ADVANCING ZINC FINGER NUCLEASES FOR TARGETED GENOME MANIPULATIONR01GM088040 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH, PETERSON, RANDALL T · 2009 to 2016
$4.5M
Dissecting the Genetics of Human Hemostatic Disorders Using ZebrafishR01HL124232 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHAVIT, JORDAN A · 2015 to 2019
$1.9M
Training Program in Translational Cardiovascular Research and EntrepreneurshipT32HL125242 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MICHELE, DANIEL E · 2015 to 2024
$1.9M
Identification of novel therapeutics for hemostatic disorders using zebrafishR01HL125774 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHAVIT, JORDAN A · 2018 to 2020
$899k
NHLBI NIH HHS R01 HL124232NHLBI NIH HHS R01 HL125774NHLBI NIH HHS T32 HL125242NIGMS NIH HHS R01 GM088040NIGMS NIH HHS T32 GM007863
6 · The paper itself

Abstract

The ability to prevent blood loss in response to injury is a conserved function of all vertebrates. Complete deficiency of the central clotting enzyme prothrombin has never been observed in humans and is incompatible with postnatal life in mice, thus limiting the ability to study its role in vivo. Zebrafish are able to tolerate severe hemostatic deficiencies that are lethal in mammals. We have generated a targeted genetic deletion in the kringle 1 domain of zebrafish prothrombin. Homozygous mutant embryos develop normally into the mid-juvenile stage but demonstrate complete mortality by 2 months of age primarily due to internal hemorrhage. Mutants are unable to form occlusive venous and arterial thrombi in response to endothelial injury, a defect that was phenocopied using direct oral anticoagulants. Human prothrombin engineered with the equivalent mutation exhibits a severe reduction in secretion, thrombin generation, and fibrinogen cleavage. Together, these data demonstrate the conserved function of thrombin in zebrafish and provide insight into the role of kringle 1 in prothrombin maturation and activity. Understanding how zebrafish are able to develop normally and survive into early adulthood without thrombin activity will provide important insight into its pleiotropic functions as well as the management of patients with bleeding disorders.

Indexed as

MutationProthrombinZebrafishZebrafish ProteinsAnimalsMiceProtein DomainsProthrombinZebrafish Proteins

Identifiers

PMID32132579
PMCPMC7055286
OpenAlexW3010102970

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.