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

• DOI: 10.1126/science.277.5323.232
• Publication Date: 2002-07-27T09:44:47Z
• Authors: Stacie K. Loftus; Jill A. Morris; Eugene D. Carstea; Jessie Z. Gu; Christiano Cummings; Anthony Brown; Jane Ellison; Kousaku Ohno; Melissa A. Rosenfeld; Danilo A. Tagle; Peter G. Pentchev; William J. Pavan
• Keywords: NPC1; Patched

An integrated human-mouse positional candidate approach was used to identify the gene responsible for phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology putative transmembrane domains Hedgehog signaling molecule Patched, cholesterol-sensing regions 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating (SCAP), orthologs identified human, nematode Caenorhabditis elegans , yeast Saccharomyces cerevisiae . may provide an important resource studying role cholesterol homeostasis neurodegeneration assessing efficacy new drugs NP-C