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

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dc.contributor.authorDurán, Anyelo
dc.contributor.authorPriestman, David
dc.contributor.authorLas Heras, Macarena
dc.contributor.authorRebolledo, Boris
dc.contributor.authorOlguín, Valeria
dc.contributor.authorCalderón, Juan
dc.contributor.authorZanlungo, Silvana
dc.contributor.authorGutiérrez, Jaime
dc.contributor.authorPlatt, Frances
dc.contributor.authorKlein, Andrés
dc.date.accessioned2023-03-20T19:57:58Z
dc.date.available2023-03-20T19:57:58Z
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.description.versionVersión publicada
dc.identifier.citationDurán, A.; Priestman, D.A.; Las Heras, M.; Rebolledo-Jaramillo, B.; Olguín, V.; Calderón, J.F.; Zanlungo, S.; Gutiérrez, J.; Platt, F.M.; Klein, A.D. A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids. Int. J. Mol. Sci. 2023, 24, 4915. https://doi.org/10.3390/ijms24054915
dc.identifier.doihttps://doi.org/10.3390/ijms24054915
dc.identifier.urihttps://repositorio.udd.cl/handle/11447/7114
dc.language.isoen
dc.subjectMetabolism
dc.subjectLysosomal enzymes
dc.subjectGlycosphingolipids
dc.subjectSystems genetics
dc.subjectModifier genes
dc.titleA Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids
dc.typeArticle
dcterms.accessRightsAcceso abierto
dcterms.sourceInternational journal of molecular sciences

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