FB2021_01, released Feb 18, 2021

Allele: Dmel\Npc1a2

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General Information
Symbol
Dmel\Npc1a2
Species
D. melanogaster
Name
FlyBase ID
FBal0189647
Feature type
allele
Associated gene
Dmel\Npc1a
Associated Insertion(s)
Carried in Construct
Allele class

loss of function allele

Mutagen
Nature of the Allele
Allele class

loss of function allele

(Huang et al., 2005)
Mutagen
Delta2-3 transposase
(Huang et al., 2005)
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DDBJ / EMBL / GenBank
DNA sequence
Protein sequence
 
UniProtKB/Swiss-Prot
    UniProtKB/TrEMBL
       
      Progenitor genotype
      P{SUPor-P}KG05670
      (Huang et al., 2005)
      Cytology
      Nature of the lesion
      Statement
      Reference

      Large deletion spanning the first exon to the fifth exon of Npc1a.

      (Xiang et al., 2010)

      Imprecise excision of the P{SUPor-P} element results in deletion of part of the NPC1 gene, resulting in an expressed protein product which lacks the 45 N-terminal amino acid residues.

      (Huang et al., 2005)
      Expression Data
      Reporter Expression
      Additional Information
      Statement
      Reference
       
      Marker for
      Reflects expression of
      Reporter construct used in assay
      Human Disease Associations
      Disease Ontology (DO) Annotations
      Models Based on Experimental Evidence ( 1 )
      Disease
      Evidence
      References
      model of  Niemann-Pick disease
      CEA
      (Huang et al., 2005)
      CEA with Npc1aUAS.EYFP
      (Huang et al., 2005)
      Modifiers Based on Experimental Evidence ( 0 )
      Disease
      Interaction
      References
      Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
       

      The Npc1a2 mutant alone can be used to recapitulate developmental phenotypes, but as these flies are lethal it is not possible to use this model to look at adults. Overexpressing Npc1aScer\UAS.T:Avic\GFP-EYFP in the ring gland is sufficient to overcome this lethality, producing a model that can be used to examine phenotypes in various adult tissues.

      (Huang et al., 2005)
      Phenotypic Data
      Phenotypic Class
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      NPC12 mutants remain as first-instar larvae for a prolonged period before dying 90-192 hours AEL. NPC12 first instar larvae show aberrant subcellular sterol accumulation. The first instar arrest can be partially rescued by feeding the larvae with 20E; when 20E is fed at 26 hours AEL, only 25% die during the first instar, 29% die during the transition to the second instar, 45% die in the second instar and 2% die in the third instar. When 20E is fed at 40 hours AEL, there is a weaker rescue. The first instar arrest can be significantly rescued by increasing the amount of cholesterol (which allows some survival to the pupal stage) or 7-dehydrocholesterol (which allows some survival to the adult stage) in the larval food. However, increasing the level of ergosterol, feeding larvae with desmosterol, or feeding with progesterone, does not rescue the larval lethality. Brains from 96 hour AEL NPC12 first-instar mutants show normal morphology with no evidence of neurodegenerative vacuoles.

      (Huang et al., 2005)
      External Data
      Interactions
      Show genetic interaction network for Enhancers & Suppressors
      Phenotypic Class
      Phenotype Manifest In
      Additional Comments
      Genetic Interactions
      Statement
      Reference
      Xenogenetic Interactions
      Statement
      Reference
      Complementation and Rescue Data
      Rescued by

      Npc1a2 is rescued by Npc1aUAS.EYFP/Scer\GAL469B

      (Huang et al., 2005)

      Npc1a2 is rescued by Npc1aUAS.EYFP/Scer\GAL4Tub.PU

      (Huang et al., 2005)
      Partially rescued by

      Npc1a2 is partially rescued by Scer\GAL42-286/Npc1aUAS.EYFP

      (Huang et al., 2005)

      Npc1a2 is partially rescued by Scer\GAL4Feb36/Npc1aUAS.EYFP

      (Huang et al., 2005)
      Not rescued by

      Npc1a2 is not rescued by Npc1aUAS.EYFP/Scer\GAL448Y

      (Huang et al., 2005)

      Npc1a2 is not rescued by Scer\GAL4Aug21/Npc1aUAS.EYFP

      (Huang et al., 2005)

      Npc1a2 is not rescued by Scer\GAL4Mhc.PW/Npc1aUAS.EYFP

      (Huang et al., 2005)

      Npc1a2 is not rescued by Scer\GAL4elav-C155/Npc1aUAS.EYFP

      (Huang et al., 2005)
      Comments

      Expression of NPC1Scer\UAS.T:Avic\GFP-EYFP in the ring and salivary glands, driven by Scer\GAL42-286, rescues the lethality of NPC12 mutants, allowing them to survive to adulthood. The subcellular accumulation of sterols in many tissues other than the ring gland is not reduced in the rescued mutants. Sterol accumulation is most severe in the Malpighian tubules, which show ultrastructural defects. Expression of NPC1Scer\UAS.T:Avic\GFP-EYFP in the ring gland, salivary glands, trachea, midgut and Malpighian tubules, driven by Scer\GAL4Feb36, also rescues NPC12 lethality, although some mutants still die as third instar larvae.

      (Huang et al., 2005)
      Images (0)
      Mutant
      Wild-type
      Stocks (1)
      Notes on Origin
      Discoverer
      External Crossreferences and Linkouts ( 0 )
      Synonyms and Secondary IDs (4)
      Reported As
      Symbol Synonym
      NPC12
      Npc1a2
      dncp1a2
      (Huang et al., 2005)
      npc12
      (Xiang et al., 2010)
      Name Synonyms
      Secondary FlyBase IDs
        References (2)