Evidence map›Paper›PMID 33986446›Full record

ArticleScientific reports2021

Quantitative trait locus mapping identifies the Gpnmb gene as a modifier of mouse macrophage lysosome function.

Peggy Robinet, Brian Ritchey, Shuhui Wang Lorkowski, Alexander M Alzayed, Sophia DeGeorgia, Eve Schodowski, C Alicia Traughber, Jonathan D Smith

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
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  8. Membrane-boundeLife · 2024
    Article
  9. Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  10. Review
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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.

Peggy Robinet *Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Brian Ritchey *Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Shuhui Wang Lorkowski *Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Alexander M AlzayedDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Sophia DeGeorgiaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Eve SchodowskiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
C Alicia TraughberDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Jonathan D SmithDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. smithj4@ccf.org.ORCID 0000-0002-0415-386X
Cleveland Clinic Lerner College of Medicine · US

Funding

Vascular Cell function and AtherosclerosisP01HL029582 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 1985 to 2019
$32.0M
NHLBI NIH HHS P01 HL029582NIH HHS P01HL029582
6 · The paper itself

Abstract

We have previously shown that the DBA/2J versus AKR/J mouse strain is associated with decreased autophagy-mediated lysosomal hydrolysis of cholesterol esters. Our objective was to determine differences in lysosome function in AKR/J and DBA/2J macrophages, and identify the responsible genes. Using a novel dual-labeled indicator of lysosome function, DBA/2J versus AKR/J bone marrow derived macrophages had significantly decreased lysosome function. We performed quantitative trait loci mapping of lysosome function in bone marrow macrophages from an AKR/J × DBA/2J strain intercross. Four distinct lysosome function loci were identified, which we named macrophage lysosome function modifier (Mlfm) Mlfm1 through Mlfm4. The strongest locus Mlfm1 harbors the Gpnmb gene, which has been shown to recruit autophagy protein light chain 3 to autophagosomes for lysosome fusion. The parental DBA/2J strain has a nonsense variant in Gpnmb. siRNA knockdown of Gpnmb in AKR/J macrophages decreased lysosome function, and Gpnmb deletion through CRISP/Cas9 editing in RAW 264.7 mouse macrophages also demonstrated a similar result. Furthermore, a DBA/2 substrain, called DBA/2J-Gpnmb+/SjJ, contains the wildtype Gpnmb gene, and macrophages from this Gpnmb-preserved DBA/2 substrain exhibited recovered lysosome function. In conclusion, we identified Gpnmb as a causal modifier gene of lysosome function in this strain pair.

Indexed as

AnimalsChromosome MappingEye ProteinsFemaleGenes, ModifierLysosomesMacrophagesMaleMembrane GlycoproteinsMiceMice, Inbred AKRMice, Inbred DBAQuantitative Trait LociEye ProteinsGpnmb protein, mouseMembrane Glycoproteins

Identifiers

PMID33986446
PMCPMC8119501
OpenAlexW3163495944

What OpenQuestion holds

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Registered trials

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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.