A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids

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dc.contributor.authorDuran, Anyelo
dc.contributor.authorPriestman, David A.
dc.contributor.authorLas Heras, Macarena
dc.contributor.authorRebolledo-Jaramillo, Boris
dc.contributor.authorOlguin, Valeria
dc.contributor.authorCalderon, Juan F.
dc.contributor.authorZanlungo, Silvana
dc.contributor.authorGutierrez, Jaime
dc.contributor.authorPlatt, Frances M.
dc.contributor.authorKlein, Andres D.
dc.date.accessioned2025-01-20T20:16:34Z
dc.date.available2025-01-20T20:16:34Z
dc.date.issued2023
dc.description.abstractIdentification of genetic modulators of lysosomal enzyme activities and glycosphingolipids (GSLs) may facilitate the development of therapeutics for diseases in which they participate, including Lysosomal Storage Disorders (LSDs). To this end, we used a systems genetics approach: we measured 11 hepatic lysosomal enzymes and many of their natural substrates (GSLs), followed by modifier gene mapping by GWAS and transcriptomics associations in a panel of inbred strains. Unexpectedly, most GSLs showed no association between their levels and the enzyme activity that catabolizes them. Genomic mapping identified 30 shared predicted modifier genes between the enzymes and GSLs, which are clustered in three pathways and are associated with other diseases. Surprisingly, they are regulated by ten common transcription factors, and their majority by miRNA-340p. In conclusion, we have identified novel regulators of GSL metabolism, which may serve as therapeutic targets for LSDs and may suggest the involvement of GSL metabolism in other pathologies.
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms24054915
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://doi.org/10.3390/ijms24054915
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92338
dc.identifier.wosidWOS:000947963800001
dc.issue.numero5
dc.language.isoen
dc.revistaInternational journal of molecular sciences
dc.rightsacceso restringido
dc.subjectmetabolism
dc.subjectlysosomal enzymes
dc.subjectglycosphingolipids
dc.subjectsystems genetics
dc.subjectmodifier genes
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleA Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids
dc.typeartículo
dc.volumen24
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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