A model for Niemann-Pick type C disease in the nematode Caenorhabditis elegans

Citation
M. Sym et al., A model for Niemann-Pick type C disease in the nematode Caenorhabditis elegans, CURR BIOL, 10(9), 2000, pp. 527-530
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
CURRENT BIOLOGY
ISSN journal
0960-9822 → ACNP
Volume
10
Issue
9
Year of publication
2000
Pages
527 - 530
Database
ISI
SICI code
0960-9822(20000504)10:9<527:AMFNTC>2.0.ZU;2-1
Abstract
Niemann-Pick type C (NP-C) disease is a progressive neurodegenerative disor der characterized by the inappropriate accumulation of unesterified cholest erol in lysosomes [1]. NP C patients show various defects including hepatos plenomegaly, ataxia, dystonia and dementia, Most cases of NP C are associat ed with inactivating mutations of the NPC1 gene [2], which encodes a protei n implicated in the retrograde transport of sterols and other cargo from ly sosomes [3]. Furthermore, localization of the NPC1 protein to lysosomal/end osomal compartments is essential for proper transport [4], To create a mode l of NP C disease in a simple, genetically tractable organism, we generated deletion mutations in two Caenorhabditis elegans homologs of the human NPC 1 gene, designated npc-l and npc-a. Animals mutant for npc-l developed slow ly, laid eggs prematurely, and were hypersensitive to cholesterol deprivati on. Furthermore, npc-l; npc-a double-mutant animals inappropriately formed dauer larvae under favorable growth conditions. These phenotypes in C. eleg ans provide a model system for both genetic and chemical suppressor screeni ng that could identify promising drug targets and leads for NP-C disease.