Identification of genetic modifiers of murine hepatic β-glucocerebrosidase activity

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dc.contributor.authorDuran, Anyelo
dc.contributor.authorRebolledo-Jaramillo, Boris
dc.contributor.authorOlguin, Valeria
dc.contributor.authorRojas-Herrera, Marcelo
dc.contributor.authorHeras, Macarena Las
dc.contributor.authorCalderon, Juan F.
dc.contributor.authorZanlungo, Silvana
dc.contributor.authorPriestman, David A.
dc.contributor.authorPlatt, Frances M.
dc.contributor.authorKlein, Andres D.
dc.date.accessioned2025-01-20T22:03:05Z
dc.date.available2025-01-20T22:03:05Z
dc.date.issued2021
dc.description.abstractThe acid beta-glucocerebrosidase (GCase) enzyme cleaves glucosylceramide into glucose and ceramide. Loss of function variants in the gene encoding for GCase can lead to Gaucher disease and Parkinson's disease. Therapeutic strategies aimed at increasing GCase activity by targeting a modulating factor are attractive and poorly explored. To identify genetic modifiers, we measured hepatic GCase activity in 27 inbred mouse strains. A genome-wide association study (GWAS) using GCase activity as a trait identified several candidate modifier genes, including Dmrtc2 and Arhgef1 (p=2.1x10(-7)), and Grik5 (p=2.1x10(-7)). Bayesian integration of the gene mapping with transcriptomics was used to build integrative networks. The analysis uncovered additional candidate GCase regulators, highlighting modules of the acute phase response (p=1.01x10(-8)), acute inflammatory response (p=1.01x10(-8)), fatty acid beta-oxidation (p=7.43x10(-5)), among others. Our study revealed previously unknown candidate modulators of GCase activity, which may facilitate the design of therapies for diseases with GCase dysfunction.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bbrep.2021.101105
dc.identifier.issn2405-5808
dc.identifier.urihttps://doi.org/10.1016/j.bbrep.2021.101105
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94015
dc.identifier.wosidWOS:000741053100005
dc.language.isoen
dc.revistaBiochemistry and biophysics reports
dc.rightsacceso restringido
dc.subjectSystems genetics
dc.subjectModifier genes
dc.subjectbeta-glucocerebrosidase
dc.subjectInbred strains
dc.subjectGaucher disease
dc.subjectParkinson's disease
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleIdentification of genetic modifiers of murine hepatic β-glucocerebrosidase activity
dc.typeartículo
dc.volumen28
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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