title: Hepatic Primary and Secondary Cholesterol Deposition and Damage in Niemann-Pick Disease.
abstract: Niemann-Pick C disease is a neurovisceral disorder caused by mutations in the NPC gene that result in systemic accumulation of intracellular cholesterol. Although neurodegeneration defines the disease's severity, in most patients it is preceded by hepatic complications such as cholestatic jaundice or hepatomegaly. To analyze the contribution of the hepatic disease in Niemann-Pick C disease progression and to evaluate the degree of primary and secondary hepatic damage, we generated a transgenic mouse with liver-selective expression of NPC1 from embryonic stages. Hepatic NPC1 re-expression did not ameliorate the onset and progression of neurodegeneration of the NPC1-null animal. However, the mice showed reduced hepatomegalia and dramatic, although not complete, reduction of hepatic cholesterol and serum bile salts, bilirubin, and transaminase levels. Therefore, hepatic primary and secondary cholesterol deposition and damage occur simultaneously during Niemann-Pick C disease progression.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona. Electronic address: martabosch@ub.edu.
authors.forename: Marta
authors.initials: M
authors.lastname: Bosch
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona.
authors.forename: Alba
authors.initials: A
authors.lastname: Fajardo
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; Departament of Cell Biology, Immunology, and Neurosciences, Facultat de Medicina, Universitat de Barcelona, Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid.
authors.forename: Rafael
authors.initials: R
authors.lastname: Alcalá-Vida
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fernández-Vidal
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; Departament of Cell Biology, Immunology, and Neurosciences, Facultat de Medicina, Universitat de Barcelona, Barcelona.
authors.forename: Francesc
authors.initials: F
authors.lastname: Tebar
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; Departament of Cell Biology, Immunology, and Neurosciences, Facultat de Medicina, Universitat de Barcelona, Barcelona.
authors.forename: Carlos
authors.initials: C
authors.lastname: Enrich
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; Hopital Clinic i Provincial de Barcelona (HCPB), Madrid; Centro de Investigación Biomédica en Red sobre of Enfermedades Raras (CIBERER), Madrid.
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; Departament of Cell Biology, Immunology, and Neurosciences, Facultat de Medicina, Universitat de Barcelona, Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid.
authors.forename: Esther
authors.initials: E
authors.lastname: Pérez-Navarro
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; Departament of Cell Biology, Immunology, and Neurosciences, Facultat de Medicina, Universitat de Barcelona, Barcelona; Institució Catalana de Recerca i Estudis avançat (ICREA), Barcelona, Spain. Electronic address: apols@ub.edu.
authors.forename: Albert
authors.initials: A
authors.lastname: Pol
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D053595:Embryonic Stem Cells; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D000637:Transaminases / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; D002784:Cholesterol; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase; D001663:Bilirubin