Evidence map›Paper›PMID 40681653›Full record

ArticleCommunications biology2025

A murine model lacking Lyst recapitulates Chediak-Higashi syndrome with an earlier-onset neurodegenerative phenotype.

Sunny Greene, Mackenzie L Talbert, F Graeme Frost, Patricia M Zerfas, Danielle Springer, Audrey Noguchi, Marie Morimoto, Dawn Maynard, Lisa Garrett, Gene Elliot and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Diffusion tensor imaging in Chediak Higashi Disease.medRxiv : the preprint server for health sciences · 2025
    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

18 authors.

Sunny GreeneHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5126-3383
Mackenzie L TalbertHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
F Graeme FrostNational Institutes of Health Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Patricia M ZerfasDiagnostic and Research Services Branch, Office of Research Services, National Institutes of Health, Bethesda, MD, USA.
Danielle SpringerMurine Phenotyping Core, National Heart Lung & Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Audrey NoguchiMurine Phenotyping Core, National Heart Lung & Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Marie MorimotoNational Institutes of Health Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Dawn MaynardHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Lisa GarrettEmbryonic Stem Cell and Transgenic Mouse Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Gene ElliotEmbryonic Stem Cell and Transgenic Mouse Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Maria TraverTwinbrook Imaging Facility, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8267-4161
David YarnellHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Petcharat LeoyklangNational Institutes of Health Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
John D BurkeHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Elena-Raluca NicoliNational Institutes of Health Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5545-630X
William A GahlHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Wendy J IntroneHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2422-9750
May Christine V MalicdanHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. maychristine.malicdan@nih.gov.ORCID http://orcid.org/0000-0003-1697-6959

Funding

U.S. Department of Health & Human Services | National Institutes of Health (NIH) Intramural Research ProgramsU.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) Intramural Research Program
6 · The paper itself

Abstract

Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder caused by pathogenic variants in the lysosomal trafficking regulator (LYST) gene and characterized by significant immunological and neurological impairment. Current mouse models do not replicate the early-onset neurological symptoms of patients. We develop and characterize a CHS model lacking the Lyst gene (ΔLYST-B6) using CRISPR-Cas9. The ΔLYST-B6 mouse exhibits key CHS features, including partial oculocutaneous albinism, prolonged bleeding, and enlarged intracellular granules. Molecular analyses confirm LYST deficiency, with reduced Lyst mRNA and protein levels across various tissues. Histological examination reveals progressive cerebellar Purkinje cell loss and axonal degeneration in peripheral nerves. Importantly, the ΔLYST-B6 show significant neurological impairment by 6 months of age. Lipidomic and transcriptomic analyses highlight increased proinflammatory lipid levels and immune signaling, suggesting neuroinflammation in CHS pathology. The ΔLYST-B6 mouse provides a valuable tool for studying the underlying mechanisms of CHS-associated neurodegeneration and for developing potential therapeutic strategies.

Indexed as

Chediak-Higashi SyndromeVesicular Transport ProteinsAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, KnockoutPhenotypePurkinje CellsVesicular Transport Proteins

Identifiers

PMID40681653
PMCPMC12274407

What OpenQuestion holds

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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.