Lack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of Niemann-Pick Type C protein-deficient mice

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dc.catalogadoryvc
dc.contributor.authorMeneses-Salas, Elsa
dc.contributor.authorGarcía-Forn, Marta
dc.contributor.authorCastany-Pladevall, Carla
dc.contributor.authorLu, Albert
dc.contributor.authorFajardo, Alba
dc.contributor.authorJosé, Jaimy
dc.contributor.authorWahba, Mohamed
dc.contributor.authorBosch, Marta
dc.contributor.authorPol, Albert
dc.contributor.authorTebar, Francesc
dc.contributor.authorKlein Posternack, Andrés David
dc.contributor.authorZanlungo Matsuhiro, Silvana
dc.contributor.authorPérez-Navarro, Esther
dc.contributor.authorGrewal, Thomas
dc.contributor.authorEnrich, Carlos
dc.contributor.authorRentero, Carles
dc.date.accessioned2024-06-06T19:19:44Z
dc.date.available2024-06-06T19:19:44Z
dc.date.issued2020
dc.description.abstractNiemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by cholesterol accumulation caused by loss-of-function mutations in the Npc1 gene. NPC disease primarily affects the brain, causing neuronal damage and affecting motor coordination. In addition, considerable liver malfunction in NPC disease is common. Recently, we found that the depletion of annexin A6 (ANXA6), which is most abundant in the liver and involved in cholesterol transport, ameliorated cholesterol accumulation in Npc1 mutant cells. To evaluate the potential contribution of ANXA6 in the progression of NPC disease, double-knockout mice (Npc1-/-/Anxa6-/-) were generated and examined for lifespan, neurologic and hepatic functions, as well as liver histology and ultrastructure. Interestingly, lack of ANXA6 in NPC1-deficient animals did not prevent the cerebellar degeneration phenotype, but further deteriorated their compromised hepatic functions and reduced their lifespan. Moreover, livers of Npc1-/-/Anxa6-/- mice contained a significantly elevated number of foam cells congesting the sinusoidal space, a feature commonly associated with inflammation. We hypothesize that ANXA6 deficiency in Npc1-/- mice not only does not reverse neurologic and motor dysfunction, but further worsens overall liver function, exacerbating hepatic failure in NPC disease.
dc.fechaingreso.objetodigital2025-01-07
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.ajpath.2020.12.009
dc.identifier.urihttps://doi.org/10.1016/j.ajpath.2020.12.009
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86569
dc.identifier.wosidWOS:000632503000006
dc.information.autorucFacultad de Ciencias Biológicas;Klein Posternack, Andrés David;S/I;2966
dc.information.autorucEscuela de Medicina;Zanlungo Matsuhiro, Silvana;0000-0001-8383-9829;72650
dc.language.isoen
dc.nota.accesocontenido completo
dc.rightsacceso abierto
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleLack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of Niemann-Pick Type C protein-deficient mice
dc.typeartículo
sipa.codpersvinculados72650
sipa.trazabilidadORCID;2024-06-03
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