Murine model of Niemann-Pick C disease: Mutation in a cholesterol homeostasis gene

被引：695

作者：

Loftus, SK

Morris, JA

Carstea, ED

Gu, JZ

Cummings, C

Brown, A

Ellison, J

Ohno, K

Rosenfeld, MA

Tagle, DA

Pentchev, PG

Pavan, WJ

机构：

[1] NIH, NATL HUMAN GENOME RES INST, LAB GENET DIS RES, BETHESDA, MD 20892 USA

[2] NINCDS, NATL HUMAN GENOME RES INST, NIH, BETHESDA, MD 20892 USA

[3] NINCDS, DEV & METAB NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA

[4] TOTTORI UNIV, FAC MED, SCH LIFE SCI, YONAGO, TOTTORI 683, JAPAN

来源：

SCIENCE | 1997年 / 277卷 / 5323期

关键词：

D O I：

10.1126/science.277.5323.232

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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页码：232 / 235

页数：4

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