ArticleScientific reports2021
Quantitative trait locus mapping identifies the Gpnmb gene as a modifier of mouse macrophage lysosome function.
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.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB): A Translational Pharmacodynamic Biomarker for PIKfyve Inhibition With VRG50635.Clinical and translational science · 2026Trial
- Scalable longitudinal imaging and transcriptomics of cells in dynamic enclosures.bioRxiv : the preprint server for biology · 2026Article
- GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis.Science advances · 2025Article
- Bidirectional regulation of glycoprotein nonmetastatic melanoma protein B by β-glucocerebrosidase deficiency inbioRxiv : the preprint server for biology · 2025Article
- Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures.PLoS biology · 2025Article
- Spatiotemporal transcriptomic mapping of regenerative inflammation in skeletal muscle reveals a dynamic multilayered tissue architecture.The Journal of clinical investigation · 2024Article
- The E3 ubiquitin-protein ligase UHRF1 promotes adipogenesis and limits fibrosis by suppressing GPNMB-mediated TGF-β signaling.Scientific reports · 2024Article
- Membrane-boundeLife · 2024Article
- 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 · 2024Review
- Selective dopaminergic vulnerability in Parkinson's disease: new insights into the role of DAT.Frontiers in neuroscience · 2023Review
- The physiological and pathophysiological roles of the autophagy lysosomal system in the conventional aqueous humor outflow pathway: More than cellular clean up.Progress in retinal and eye research · 2022Review
- Neurodegenerative phagocytes mediate synaptic stripping in Neuro-HIV.Brain : a journal of neurology · 2022Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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.
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