{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:41:57Z","timestamp":1790847717916,"version":"4.1.0"},"reference-count":44,"publisher":"The Company of Biologists","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,15]]},"abstract":"<jats:p>Niemann-Pick type C (NPC) disease is a fatal autosomal-recessive neurodegenerative disorder characterized by the inappropriate accumulation of unesterified cholesterol in aberrant organelles. The disease is due to mutations in either of two genes, NPC1, which encodes a transmembrane protein related to the Hedgehog receptor Patched, and NPC2, which encodes a secreted cholesterol-binding protein. Npc1 mutant mice can be partially rescued by treatment with specific steroids. We have created a Drosophila NPC model by mutating dnpc1a, one of two Drosophila genes related to mammalian NPC1. Cells throughout the bodies of dnpc1a mutants accumulated sterol in a punctate pattern, as in individuals with NPC1 mutations. The mutants developed only to the first larval stage and were unable to molt. Molting after the normal first instar period was restored to various degrees by feeding the mutants the steroid molting hormone 20-hydroxyecdysone, or the precursors of ecdysone biosynthesis, cholesterol and 7-dehydrocholesterol. dnpc1ais normally highly expressed in the ecdysone-producing ring gland. Ring gland-specific expression of dnpc1a in otherwise mutant flies allowed development to adulthood, suggesting that the lack of ecdysone in the mutants is the cause of death. We propose that dnpc1a mutants have sterols trapped in aberrant organelles, leading to a shortage of sterol in the endoplasmic reticulum and\/or mitochondria of ring gland cells, and,consequently, inadequate ecdysone synthesis.<\/jats:p>","DOI":"10.1242\/dev.02079","type":"journal-article","created":{"date-parts":[[2005,10,13]],"date-time":"2005-10-13T00:13:31Z","timestamp":1129162411000},"page":"5115-5124","source":"Crossref","is-referenced-by-count":139,"title":["A <i>Drosophila<\/i> model of the Niemann-Pick type C lysosome storage disease: <i>dnpc1a<\/i> is required for molting and sterol homeostasis"],"prefix":"10.1242","volume":"132","author":[{"given":"Xun","family":"Huang","sequence":"first","affiliation":[{"name":"Departments of Developmental Biology, Genetics, and Bioengineering, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaye","family":"Suyama","sequence":"additional","affiliation":[{"name":"Departments of Developmental Biology, Genetics, and Bioengineering, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Departments of Developmental Biology, Genetics, and Bioengineering, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Scott","sequence":"additional","affiliation":[{"name":"Departments of Developmental Biology, Genetics, and Bioengineering, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042605185864600_REF1","unstructured":"Akaboshi, S. and Ohno, K. 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E., Davies, J. P., Chen, F. W. and Ioannou, Y. A. (1999). Niemann-Pick C1 is a late endosome-resident protein that transiently associates with lysosomes and the trans-Golgi network. Mol. Genet. Metab.68, 1-13.","DOI":"10.1006\/mgme.1999.2882"},{"key":"2021042605185864600_REF15","doi-asserted-by":"crossref","unstructured":"Hooper, J. E. and Scott, M. P. (2005). Communicating with Hedgehogs. Nat. Rev. Mol. Cell. Biol.6,306-317.","DOI":"10.1038\/nrm1622"},{"key":"2021042605185864600_REF16","doi-asserted-by":"crossref","unstructured":"Ko, D. C., Gordon, M. D., Jin, J. Y. and Scott, M. P.(2001). Dynamic movements of organelles containing Niemann-Pick C1 protein: NPC1 involvement in late endocytic events. Mol. Biol. Cell12,601-614.","DOI":"10.1091\/mbc.12.3.601"},{"key":"2021042605185864600_REF17","doi-asserted-by":"crossref","unstructured":"Ko, D. C., Binkley, J., Sidow, A. and Scott, M. P.(2003). 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