Allele Dmel\Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}

General Information
Symbol	Dmel\Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}	Species	D. melanogaster
Name		FlyBase ID	FBal0190532
Feature type	allele	Associated gene	Dmel\Npc1a

Allele class
Mutagen	in vitro construct - regulatory fusion, in vitro construct - coding region fusion
Recent Updates
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FB2013_03
FB2013_02
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Nature of the Allele
Allele class
Mutagen	in vitro construct - coding region fusion (Huang et al., 2005) in vitro construct - regulatory fusion (Huang et al., 2005)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Construct: Scer\UAS regulatory sequences drive expression of full-length NPC1, which is tagged T:Avic\GFP^EYFP. (Huang et al., 2005)
Carried in construct	P{UAS-NPC1.YFP} (Huang et al., 2005, Phillips et al., 2008, Wang et al., 2011)
Tagged with	T:Avic\GFP^EYFP (Huang et al., 2005)
Cytology
Phenotypic Data
Phenotypic Class
	male sterile, with Npc1a^unspecified, Scer\GAL4^2-286 (Wang et al., 2011)
Phenotype Manifest In
	individualization stage spermatid, with Npc1a^unspecified, Scer\GAL4^2-286 (Wang et al., 2011) seminal vesicle, with Npc1a^unspecified, Scer\GAL4^2-286 (Wang et al., 2011) sperm individualization complex, with Npc1a^unspecified, Scer\GAL4^2-286 (Wang et al., 2011)
Detailed Description
	Statement Reference Npc1a[unspecified] males in which lethality has been rescued by expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of Scer\GAL4[2-286] are sterile. The seminal vesicles of the mutant males are much smaller than wild type and contain essentially no mature sperm, but an accumulation of sperm debris is seen in the basal region of the testis. A mild cytokinesis defect (penetrance 5.79%) is seen, but the mutants have a similar number of spermatids per cyst as wild type at the elongated stage. The individualisation complex assembles normally at the head region of the spermatid bundle in the mutant males. However, it gradually disintegrates as it moves along the cyst and scattered actin cones are seen. Some sperm nuclei are scattered along the cyst in the mutant males (in wild-type males they are clustered at the head of the cyst) and these scattered sperm nuclei lose their needle-like shape, becoming more condensed and rounded the further away from the head region they are. 28 +/- 16% of mutant spermatids show defects in individualisation and the average number of spermatids per cyst after individualisation is reduced to 54. Mutant spermatocytes show sterol accumulation and sterol trafficking defects. Individualisation defects are more severe at higher temperatures. The fertility of Npc1a[unspecified] males in which lethality has been rescued by expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of Scer\GAL4[2-286] is significantly increased by addition of 7-dehydrocholesterol in the food, but is not increased by the addition of cholesterol, ergosterol or sitosterol in the food. (Wang et al., 2011)
External Data
Linkouts
Interactions
Phenotypic Class
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement Reference
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Rescues	Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^69B rescues Npc1a¹ (Huang et al., 2005) Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^69B rescues Npc1a² (Huang et al., 2005) Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^Hsp83.PA rescues Npc1a^unspecified (Wang et al., 2011) Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^tub.PU rescues Npc1a¹ (Huang et al., 2005) Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^tub.PU rescues Npc1a² (Huang et al., 2005) Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^tub.PU rescues Npc1a^unspecified (Wang et al., 2011)
Partially rescues	Scer\GAL4^2-286/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} partially rescues Npc1a¹ (Huang et al., 2005, Phillips et al., 2008) Scer\GAL4^2-286/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} partially rescues Npc1a² (Huang et al., 2005) Scer\GAL4^2-286/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} partially rescues Npc1a^unspecified (Wang et al., 2011) Scer\GAL4^elav-C155/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} partially rescues Npc1a¹ (Phillips et al., 2008) Scer\GAL4^Feb36/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} partially rescues Npc1a¹ (Huang et al., 2005) Scer\GAL4^Feb36/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} partially rescues Npc1a² (Huang et al., 2005)
Fails to rescue	Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^48Y fails to rescue Npc1a¹ (Huang et al., 2005) Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^48Y fails to rescue Npc1a² (Huang et al., 2005) Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}/Scer\GAL4^repo fails to rescue Npc1a¹ (Phillips et al., 2008) Scer\GAL4^Aug21/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a¹ (Huang et al., 2005) Scer\GAL4^Aug21/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a² (Huang et al., 2005) Scer\GAL4^C587/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a^unspecified (Wang et al., 2011) Scer\GAL4^elav-C155/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a¹ (Huang et al., 2005) Scer\GAL4^elav-C155/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a² (Huang et al., 2005) Scer\GAL4^Mhc.PW/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a¹ (Huang et al., 2005) Scer\GAL4^Mhc.PW/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a² (Huang et al., 2005) Scer\GAL4^ptc-559.1/Npc1a^{Scer\UAS.T:Avic\GFP-EYFP} fails to rescue Npc1a^unspecified (Wang et al., 2011)
Comments	Expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of Scer\GAL4[2-286] partially rescues the Npc1a[unspecified] phenotype; animals are rescued to adulthood, but only 13.3% of the rescued males are fertile, and those that are fertile produce a smaller number of progeny than normal. Expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of either Scer\GAL4[Hsp83.PA] or Scer\GAL4[tub.PU] rescues the lethality of Npc1a[unspecified] animals and results in fertile males. Expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of either Scer\GAL4[C587] or Scer\GAL4[ptc-559.1] rescues the lethality of Npc1a[unspecified] animals but results in sterile males. (Wang et al., 2011) Neural expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of Scer\GAL4[elav-C155] does not rescue the ecdysone-dependent larval lethality of Npc1a[1] mutants. However, in cholesterol-rescued adult mutants, targeted neuronal expression strongly rescues the progressive movement defects and early lethality, extending the life span of Npc1a[1] mutants to a comparable age as controls. Neuronal expression also rescues the filipin-positive cholesterol aggregates found in Npc1a[1] mutant brains. Glial expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of Scer\GAL4[repo] does not rescue the ecdysone-dependent larval lethality of Npc1a[1] mutants. However, in cholesterol-rescued adult mutants, targeted glial expression strongly rescues the progressive movement defects and early lethality, extending the life span of Npc1a[1] mutants. However, Scer\GAL4[repo] controls also exhibit a longer life span, although not as long as those expressing Npc1a[Scer\UAS.T:Avic\GFP-EYFP]. Expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] in the ring gland under the control of Scer\GAL4[2-286] rescues larval lethality in Npc1a[1] mutants without cholesterol feeding but does not rescue the filipin-positive cholesterol aggregates found in Npc1a[1] mutant brains. Neural expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of Scer\GAL4[elav-C155] rescues rhabdomere structure and photoreceptor vacuolization. Neural expression of Npc1a[Scer\UAS.T:Avic\GFP-EYFP] under the control of Scer\GAL4[elav-C155] at day 45 results in a striking reduction in multi-lamellar bodies within the cytoplasm of Npc1a[1] mutant neuronal cells. (Phillips et al., 2008) Expression of NPC1^{Scer\UAS.T:Avic\GFP-EYFP} in the ring and salivary glands, driven by Scer\GAL4^2-286, rescues the lethality of NPC1¹ and 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 NPC1^{Scer\UAS.T:Avic\GFP-EYFP} in the ring gland, salivary glands, trachea, midgut and Malpighian tubules, driven by Scer\GAL4^Feb36, also rescues NPC1¹ and NPC1² lethality, although some mutants still die as third instar larvae. (Huang et al., 2005)
Stocks ( 1 )
Bloomington	41763 w^*; P{UAS-NPC1.YFP}3
Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 2 )
Reported As
Symbol Synonym	NPC1^{Scer\UAS.T:Avic\GFP-EYFP} Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}
Name Synonym
Secondary FlyBase IDs

References ( 3 )
Research paper	Wang et al., 2011, Dev. Biol. 351(1): 146--155 The cholesterol trafficking protein NPC1 is required for Drosophila spermatogenesis. [FBrf0212972] Phillips et al., 2008, J. Neurosci. 28(26): 6569--6582 Neuronal loss of Drosophila NPC1a causes cholesterol aggregation and age-progressive neurodegeneration. [FBrf0205488] Huang et al., 2005, Development 132(22): 5115--5124 A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis. [FBrf0190297]

Allele Dmel\Npc1aScer\UAS.T:Avic\GFP-EYFP

Allele Dmel\Npc1a^{Scer\UAS.T:Avic\GFP-EYFP}