Allele Dmel\vap^KS67

General Information
Symbol	Dmel\vap^KS67	Species	D. melanogaster
Name		FlyBase ID	FBal0017844
Feature type	allele	Associated gene	Dmel\vap
Also Known As	vap¹

Allele class
Mutagen	ethyl methanesulfonate
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Nature of the Allele
Allele class
Mutagen	ethyl methanesulfonate
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 Nucleotide substitution: G?A. The point mutation in this allele creates a stop codon. The predicted protein product is truncated just before the GAP catalytic domain. (Botella et al., 2003)
Cytology
Phenotypic Data
Phenotypic Class
	fertile (Botella et al., 2003) neuroanatomy defective \| adult stage (Wentzell et al., 2012) short lived \| recessive (Botella et al., 2003)
Phenotype Manifest In
	adult brain (de Belle and Heisenberg, 1996, Botella et al., 2003, Wentzell et al., 2012) autophagic vacuole & neuron & adult brain (Botella et al., 2003) ellipsoid body (de Belle and Heisenberg, 1996) lysosome & neuron & adult brain (Botella et al., 2003) neuron & adult brain (Botella et al., 2003) nodulus (de Belle and Heisenberg, 1996) optic lobe (Botella et al., 2003)
Detailed Description
	Statement Reference 14 day old vap[KS67] mutant flies show vacuoles in all parts of the brain. These increase dramatically with age (Wentzell et al., 2012) In brain sections of 1-day-old vap^KS67 homozygous flies there is no apparent difference in morphology compared with wild type. However, ultrastructural analysis of these brains reveals the accumulation in neurons of autolysosomes and vacuoles containing whorls of membranous material as well as empty vacuoles; all signs of autophagic cell death that are absent in wild-type neurons. Brain sections of seven-day-old vap^KS67 homozygous flies show vacuolization in the optic lobe and central brain, and ultrastructural analysis reveals dying neurons with digested cytoplasm, although nuclei remain intact. By 14-days of age, brain sections of these flies have a strong spongiform appearance. Despite signs of autophagic cell death, these neurons do not express markers of cell death, an lack the normal morphological characteristics of apoptotic cells. Glial cells in the brains of these flies remain normal. The maximum lifespan of vap^KS67 homozygous flies is 25 days, compared to 90 days for wild-type controls. (Botella et al., 2003) Show significantly reduced ability to develop ethanol tolerance. (Scholz et al., 2000) Flies have a number of brain defects, the exact phenotype depending on the genetic background. In the original genetic background in which it was induced, vap^KS67 produces the following phenotype; large vacuoles are restricted to the peduncles, the ellipsoid body is open ventrally and the noduli are misshapen in many flies. When placed in a Canton S background, the peduncle-specific vacuoles are smaller than in the original genetic background, and the brain is more dissociated. The central complex defects are similar to the phenotype in the original genetic background. (de Belle and Heisenberg, 1996) Isolated as a neuro-anatomical mutant (Heisenberg and Bohl, 1979). Mutant shows vacuolar spaces at a certain depth along the pedunculi of the mushroom bodies as if extrinsic cells are undergoing degeneration. Intrinsic fibers appear continuous. Viability of mutants reduced (Heisenberg).
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement Reference vap^KS67 has neuroanatomy defective \| adult stage phenotype, suppressible by Scer\GAL4^elav-C155/Appl^{s.Scer\UAS.T:Ivir\HA1} (Wentzell et al., 2012)
Other
Statement Reference Egfr^WT.hs, vap^KS67 has lethal phenotype (Botella et al., 2003, Botella et al., 2003, Botella et al., 2003, Botella et al., 2003)
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement Reference Expression of Appl[s.Scer\UAS.T:Ivir\HA1] under the control of Scer\GAL4[elav-C155] suppresses the vacuolisation seen in vap[KS67] mutant 14 day old males. (Wentzell et al., 2012) Egfr^WT.hs is lethal in a vap^KS67 homozygous background. (Botella et al., 2003)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Rescued by	vap^KS67 is rescued by Scer\GAL4^elav-C155/vap^{Scer\UAS.T:Hsap\MYC} (Botella et al., 2003)
Comments	vap^{Scer\UAS.T:Hsap\MYC}; Scer\GAL4^elav-C155 rescues the neurodegenerative phenotype of vap^KS67 homozygous adults (assayed at 7 days old), but Gap1^EP45; Scer\GAL4^elav-C155 does not. (Botella et al., 2003)
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 2 )
Reported As
Symbol Synonym	vap¹ (Botella et al., 2003, Scholz et al., 2000, de Belle and Heisenberg, 1996, Wentzell et al., 2012) vap^KS67
Name Synonym
Secondary FlyBase IDs

References ( 4 )
Research paper	Wentzell et al., 2012, Neurobiol. Disease 46(1): 78--87 Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration. [FBrf0217742] Botella et al., 2003, Mol. Biol. Cell 14(1): 241--250 Deregulation of the Egfr/Ras signaling pathway induces age-related brain degeneration in the Drosophila mutant vap. [FBrf0155942] Scholz et al., 2000, Neuron 28(1): 261--271 Functional ethanol tolerance in Drosophila. [FBrf0131396] de Belle and Heisenberg, 1996, Proc. Natl. Acad. Sci. U.S.A. 93(18): 9875--9880 Expression of Drosophila mushroom body mutations in alternative genetic backgrounds: A case study of the mushroom body miniature gene (mbm). [FBrf0090884]

Allele Dmel\vapKS67

Allele Dmel\vap^KS67