Murine Model of Niemann-Pick C Disease: Mutation in a Cholesterol Homeostasis Gene

An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signalin...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1997-07, Vol.277 (5323), p.232-235
Main Authors: Loftus, Stacie K., Morris, Jill A., Carstea, Eugene D., Gu, Jessie Z., Cummings, Christiano, Brown, Anthony, Ellison, Jane, Ohno, Kousaku, Rosenfeld, Melissa A., Tagle, Danilo A., Pentchev, Peter G., Pavan, William J.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Biological and medical sciences
Cholangiography
Cholesterol
Cholesterol - metabolism
Cholesterols
Complementary DNA
Disease models
Disease Models, Animal
Errors of metabolism
Genes
Genetic aspects
Genetic disorders
Genetic mutation
Genetics
Genomics
Homeostasis
Humans
Hydroxymethylglutaryl CoA Reductases - chemistry
Inborn errors of metabolism
Intracellular Signaling Peptides and Proteins
Lipids (lysosomal enzyme disorders, storage diseases)
Liver
Lysosomes - metabolism
Medical disorders
Medical research
Medical sciences
Membrane Proteins - chemistry
Metabolic diseases
Metabolism, Inborn errors of
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Mutant Strains
Molecular Sequence Data
Mutation
Nervous system diseases
Niemann-Pick Diseases - genetics
Niemann-Pick Diseases - metabolism
Phenotype
Protein Sorting Signals - chemistry
Proteins - chemistry
Proteins - genetics
Proteins - physiology
Sequence Homology, Amino Acid
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Description
Summary:An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signaling molecule Patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, the nematode Caenorhabditis elegans, and the yeast Saccharomyces cerevisiae. The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.277.5323.232