Journal ArticleDOI
Identification of HE1 as the Second Gene of Niemann-Pick C Disease
Saule Naureckiene,David E. Sleat,David E. Sleat,Henry Lackland,Anthony H. Fensom,Marie T. Vanier,Robert Wattiaux,Michel Jadot,Peter Lobel,Peter Lobel +9 more
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TLDR
Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.Abstract:
Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes. Here we show that the disease is caused by a deficiency in HE1, a ubiquitously expressed lysosomal protein identified previously as a cholesterol-binding protein. HE1 was undetectable in fibroblasts from NP-C2 patients but present in fibroblasts from unaffected controls and NP-C1 patients. Mutations in the HE1 gene, which maps to chromosome 14q24.3, were found in NP-C2 patients but not in controls. Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.read more
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Lysosome motility and distribution: Relevance in health and disease.
Juan Esteban Oyarzún,Jonathan Lagos,Mary Carmen Vázquez,Cristian Valls,Catalina De la Fuente,Maria-Isabel Yuseff,Alejandra R. Alvarez,Silvana Zanlungo +7 more
TL;DR: The correct localization of lysosomes is relevant in several physiological processes, including appropriate antigen presentation, neurotransmission and receptors modulation in neuronal synapsis, whereas hepatic lysOSomes and autophagy are master regulators of nutrient homeostasis.
Journal ArticleDOI
Clinical, Electrophysiological, and Serum Biochemical Measures of Progressive Neurological and Hepatic Dysfunction in Feline Niemann-Pick Type C Disease
Charles H. Vite,Wenge Ding,Caroline Bryan,Patricia O'Donnell,Karyn Cullen,David O. Aleman,Mark E. Haskins,Thomas J. Van Winkle +7 more
TL;DR: These data are the first to document progressive hepatic disease in the feline model and demonstrate the importance of liver disease as part of the NP-C disease phenotype.
Journal ArticleDOI
Caenorhabditis elegans as a model for lysosomal storage disorders.
TL;DR: The overview of potential lysosomal phenotypes presented here might be used as a starting point for the phenotypic characterization of newly developed knock-out models or for the design of genetic screens selecting for loss or gain of suitable knock- out model phenotypes.
Journal ArticleDOI
Niemann-Pick disease type C: cataplexy and hypocretin in cerebrospinal fluid.
Katsuyuki Oyama,Tsutomu Takahashi,Yutaka Shoji,Mika Oyamada,Atsuko Noguchi,Hiroaki Tamura,Goro Takada,Takashi Kanbayashi +7 more
TL;DR: A Japanese patient with NPC caused by a homozygous c.2974 G > T mutation of the NPC1 gene, which predicts a glycine to tryptophan change at codon 992, is reported, confirming the association of reduced CSF hypocretin-1 levels with cataplexy in NPC.
Journal ArticleDOI
Npc1 deficiency in the C57BL/6J genetic background enhances Niemann-Pick disease type C spleen pathology.
Julio Parra,Andrés D. Klein,Juan Castro,María Gabriela Morales,Matias Mosqueira,Ilse Valencia,Víctor Cortés,Attilio Rigotti,Silvana Zanlungo +8 more
TL;DR: Npc1 deficiency in the C57BL6/J background is associated with spleen, erythrocyte, and immune system abnormalities that lead to a reduced lifespan and transferred the Npc1 mutation from the BALB/c to C57bl/6J inbred background was transferred.
References
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Book
The Metabolic and Molecular Bases of Inherited Disease
TL;DR: In this paper, the authors present a list of disorders of MITOCHONDRIAL FUNCTION, including the following: DISORDERS OF MIOCHONDRIC FERTILITY XIX, XVI, XIX.
Journal ArticleDOI
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Journal ArticleDOI
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
David E. Sleat,Robert J. Donnelly,Henry Lackland,Henry Lackland,Chang Gong Liu,Istvan Sohar,Istvan Sohar,Raju K. Pullarkat,Peter Lobel,Peter Lobel +9 more
TL;DR: In this paper, the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, and a single protein was identified that is absent in LINCL.
Journal ArticleDOI
Niemann–Pick C1 Is a Late Endosome-Resident Protein That Transiently Associates with Lysosomes and the Trans-Golgi Network
TL;DR: Characterizing the subcellular location of the NPC1 protein suggests that U18666A may inhibit the retrograde transport of NPC1 from lysosomes to late endosomes for subsequent transfer to the trans-Golgi network.
Journal Article
Genetic heterogeneity in Niemann-Pick C disease: a study using somatic cell hybridization and linkage analysis.
TL;DR: In this article, the authors conducted a study on skin fibroblast cultures from 32 unrelated Niemann-Pick C patients covering the range of known clinical and biochemical phenotypes.
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