PUBLICATION

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in Zebrafish

Authors
Schwend, T., Loucks, E.J., Snyder, D., and Ahlgren, S.C.
ID
ZDB-PUB-110602-8
Date
2011
Source
Journal of Lipid Research   52(7): 1328-44 (Journal)
Registered Authors
Ahlgren, Sara, Loucks, Evyn
Keywords
none
MeSH Terms
  • Cytoskeleton/drug effects
  • Cytoskeleton/metabolism
  • Membrane Proteins/chemistry
  • Membrane Proteins/deficiency
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Protein Structure, Tertiary
  • Cell Differentiation/drug effects
  • Cell Differentiation/genetics
  • Actins/metabolism
  • Molecular Sequence Data
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Humans
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Animals
  • Oligonucleotides, Antisense/genetics
  • Cholesterol/metabolism*
  • Biological Transport/drug effects
  • Biological Transport/genetics
  • Embryo, Nonmammalian/cytology*
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism*
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics
  • Cell Death/drug effects
  • Cell Death/genetics
  • Ovum/cytology
  • Ovum/drug effects
  • Gene Knockdown Techniques
  • Amino Acid Sequence
  • Cell Movement*/drug effects
  • Cell Movement*/genetics
  • Cloning, Molecular
  • Dexamethasone/pharmacology
  • Rabbits
  • Pregnenolone/pharmacology
  • Mice
(all 42)
PubMed
21576600 Full text @ J. Lipid Res.
Abstract
Niemann-Pick type C disease (NP-C), often associated with Niemann-Pick disease, type C1 (NPC1) mutations, is a cholesterol-storage disorder characterized by cellular lipid accumulation, neurodegeneration, and reduced steroid production. To study NPC1 function in vivo, we cloned zebrafish npc1, and analyzed its gene expression and activity by reducing Npc1 protein with morpholino-oligonucleotides. Filipin staining in npc1-morphant cells was punctate, suggesting abnormal accumulation of cholesterol. Developmentally, reducing Npc1 did not disrupt early cell fate or survival; however, early morphogenetic movements were delayed, and the actin cytoskeleton network was abnormal. Morpholino-induced defects were rescued with ectopic expression of mouse NPC1, demonstrating functional gene conservation, and by treatments with steroids pregnenolone or dexamethasone, suggesting that reduced steroidogenesis contributed to abnormal cell movements. Cell death was found in anterior tissues of npc1-morphants at later stages, consistent with findings in mammals. Our studies show that npc1 is required early for proper cell movements and cholesterol localization and later for cell survival.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
npc1MO1-npc1MRPHLNO
npc1MO2-npc1MRPHLNO
tp53MO4-tp53MRPHLNO
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Fish
1 - 3 of 3
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Antibodies
No data available
Orthology
Gene Orthology
npc1
1 - 1 of 1
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Engineered Foreign Genes
No data available
Mapping
No data available