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Title: | Lack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of Niemann-Pick type C protein-deficient mice |
Author: | Meneses Salas, Elsa Garcia-Forn, Marta Castany-Pladevall, Carla Lu, Albert Fajardo, Alba Jose, Jaimy Wahba, Mohamed Bosch i Rodríguez, Marta Pol i Sorolla, Albert Tebar Ramon, Francesc Klein, Andrés D. Zanlungo, Silvana Pérez-Navarro, Esther Grewal, Thomas Enrich Bastús, Carles Rentero Alfonso, Carles |
Keywords: | Colesterol Fetge Models animals en la investigació Cholesterol Liver Animal models in research |
Issue Date: | 17-Dec-2020 |
Publisher: | Elsevier |
Abstract: | Niemann-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, eurologic 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.ajpath.2020.12.009 |
It is part of: | American Journal of Pathology, 2021, vol. 191, num. 3, p. 475-486 |
URI: | http://hdl.handle.net/2445/174047 |
Related resource: | https://doi.org/10.1016/j.ajpath.2020.12.009 |
ISSN: | 0002-9440 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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