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Lack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of NPC1- deficient mice

Show simple item record Meneses-Salas, Elsa Garcia-Forn, Marta Castany-Pladevall, Carla Lu, Albert Fajardo, Alba José, Jaimy Wahba, Mohamed Bosch, Marta Pol, Albert Tebar, Francesc Klein, Andrés Zanlungo, Silvana Pérez-Navarro, Esther Grewal, Thomas Enrich, Carlos Rentero, Carles 2020-12-22T16:21:34Z 2020-12-22T16:21:34Z 2020
dc.identifier.citation Meneses-Salas E, Garcia-Forn M, Castany-Pladevall C, Lu A, Fajardo A, Jose J, Wahba M, Bosch M, Pol A, Tebar F, Klein AD, Zanlungo S, Pérez-Navarro E, Grewal T, Enrich C, Rentero C, Lack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of NPC1-deficient mice, The American Journal of Pathology (2021) es
dc.identifier.uri es
dc.description Centro de Genética y Genómica es
dc.description.abstract Niemann-Pick type C disease (NP-C) is a lysosomal storage disorder characterized by cholesterol accumulation caused by loss-of-function mutations in the Npc1 gene. NP-C disease primarily affects the brain, causing neuronal damage and affecting motor coordination. In addition, considerable liver malfunction in NP-C disease is common. Recently, we demonstrated 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 NP-C disease, double-knockout mice (Npc1-/-/Anxa6-/-) were generated and examined for lifespan, neurological and hepatic functions, as well as liver histology and ultrastructure. Strikingly, lack of ANXA6 in NPC1-deficient animals did not prevent the cerebellar degeneration phenotype but further deteriorated their compromised hepatic functions and reduced 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 do not reverse neurological and motor dysfunction and it further worsens overall liver function, exacerbating hepatic failure in NP-C disease. es
dc.language.iso en es
dc.publisher Elsevier Inc./ American Society for Investigative Pathology es
dc.subject Liver dysfunction es
dc.subject Lifespan es
dc.subject Annexin A6 es
dc.title Lack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of NPC1- deficient mice es
dc.type Article es

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