Evidence map›Paper›PMID 27073223›Full record

ArticleBlood2016

Gene disruption of dematin causes precipitous loss of erythrocyte membrane stability and severe hemolytic anemia.

Yunzhe Lu, Toshihiko Hanada, Yuko Fujiwara, Jennifer O Nwankwo, Adam J Wieschhaus, John Hartwig, Sha Huang, Jongyoon Han, Athar H Chishti

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. The Role of Liquid-Liquid Phase Separation in Actin Polymerization.International journal of molecular sciences · 2023
    Review
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  7. Self-construction of actin networks through phase separation-induced abLIM1 condensates.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Yunzhe LuDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA;ORCID 0000-0001-7542-6848
Toshihiko HanadaDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA;
Yuko FujiwaraDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Hematology/Oncology, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA;
Jennifer O NwankwoDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA; Pharmacology & Experimental Therapeutics, Tufts University School of Medicine, Boston, MA;
Adam J WieschhausDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA;
John HartwigDivision of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
Sha HuangDepartment of Electrical Engineering and Computer Science and.
Jongyoon HanDepartment of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; and.
Athar H ChishtiDepartment of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA; Pharmacology & Experimental Therapeutics, Tufts University School of Medicine, Boston, MA; Sackler School of Graduate Biomedical Sciences, Programs in Cellular and Molecular Physiology, and Department of Molecular Microbiology, Tufts University School of Medicine, Boston, MA.ORCID 0000-0003-0335-1861
Tufts University · USBoston Children's Hospital · USBrigham and Women's Hospital · USMassachusetts Institute of Technology · US

Funding

High-throughput targeted mutagenesis of mouse stem cell linesU01HG004080 · NHGRI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI DE JONG, PIETER J. · 2006 to 2010
$28.1M
Production of Targeted Null Mutations for 10,000 Genes in C57BL/6 ES CellsU01HG004085 · NHGRI · REGENERON PHARMACEUTICALS, INC. · PI VALENZUELA, DAVID MANUEL · 2006 to 2010
$25.3M
UCD KOMP PROJECT REPOSITORYU42RR024244 · NCRR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2007 to 2010
$7.9M
Role of erythrocyte band 3 in malaria adhesionR01HL060961 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHISHTI, ATHAR H. · 1998 to 2023
$5.9M
Project-002U54DK110805 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ORKIN, STUART H, ZON, LEONARD IRA · 2016 to 2020
$5.9M
FUNCTIONAL STUDIES OF RED BLOOD CELL DEMATINR01HL051445 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHISHTI, ATHAR H. · 1994 to 2010
$1.9M
Cytoskeletal Regulation of Erythrocyte Glucose Transporter-1R01HL095050 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHISHTI, ATHAR H. · 2009 to 2012
$1.6M
Functional Studies of Erythrocyte DematinR56HL051445 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHISHTI, ATHAR H. · 2008 to 2008
$393k
Howard Hughes Medical InstituteNCRR NIH HHS U42 RR024244NHGRI NIH HHS U01 HG004080NHGRI NIH HHS U01 HG004085NHLBI NIH HHS R01 HL051445NHLBI NIH HHS R01 HL060961NHLBI NIH HHS R01 HL095050NHLBI NIH HHS R56 HL051445NIDDK NIH HHS U54 DK110805
6 · The paper itself

Abstract

Dematin is a relatively low abundance actin binding and bundling protein associated with the spectrin-actin junctions of mature erythrocytes. Primary structure of dematin includes a loosely folded core domain and a compact headpiece domain that was originally identified in villin. Dematin's actin binding properties are regulated by phosphorylation of its headpiece domain by cyclic adenosine monophosphate-dependent protein kinase. Here, we used a novel gene disruption strategy to generate the whole body dematin gene knockout mouse model (FLKO). FLKO mice, while born at a normal Mendelian ratio, developed severe anemia and exhibited profound aberrations of erythrocyte morphology and membrane stability. Having no apparent effect on primitive erythropoiesis, FLKO mice show significant enhancement of erythroblast enucleation during definitive erythropoiesis. Using membrane protein analysis, domain mapping, electron microscopy, and dynamic deformability measurements, we investigated the mechanism of membrane instability in FLKO erythrocytes. Although many membrane and cytoskeletal proteins remained at their normal levels, the major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLKO erythrocytes. Our results demonstrate that dematin plays a critical role in maintaining the fundamental properties of the membrane cytoskeleton complex.

Indexed as

Anemia, HemolyticCytoskeletonErythrocyte MembraneGene DeletionAdducinsAnimalsCalmodulin-Binding ProteinsCytoskeletal ProteinsFemaleMaleMiceMice, KnockoutSpectrinAdducinsCalmodulin-Binding ProteinsCytoskeletal ProteinsDmtn protein, mouseSpectrin

Identifiers

PMID27073223
PMCPMC4937361
OpenAlexW2340423587

What OpenQuestion holds

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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.