Maladie de Niemann-Pick type ?C? de Crocker

Pellissier, J. F.; Hassoun, Jacques; Gambarelli, D.; Bryon, Paul‐André; Casanova, Pablo González; Toga, M

doi:10.1007/bf00684945

Cited by 15 publications

(2 citation statements)

References 18 publications

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“…The multi-lamellar structures are likely to correspond to the sterol accumulation observed in the light microscope after filipin staining. Multi-lamellar structures have been observed in samples from individuals with NPC1 mutations (Pellissier et al, 1976). Excess sterol that accumulates because of lipid trafficking defects may be stored in similar aberrant organelles in Drosophila and mammals.…”

Section: Dnpc1a Is Required In Ring Gland For Larval Developmentmentioning

confidence: 99%

A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis

et al. 2005

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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.

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Section: Dnpc1a Is Required In Ring Gland For Larval Developmentmentioning

confidence: 99%

A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis

et al. 2005

View full text Add to dashboard Cite

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“…The hepatosplenomegaly varies not only between patients but also in time in individual patients, even regression having been described. 4 Vertical supranuclear opthalmoplegia is a common later finding and may be the key to the clinical diagnosis.' Usually predominantly affecting downwards saccades, the disease may also be associated with a selective disorder of vertical pursuit eye movements and defects of horizontal eye movement, and supranuclear convergence defects have been described.…”

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confidence: 99%