Open Close
General Information
Symbol
Dmel\Npc1a2
Species
D. melanogaster
Name
FlyBase ID
FBal0189647
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

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

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.

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
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.

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.

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
Partially rescued by
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.

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
Name Synonyms
Secondary FlyBase IDs
    References (2)