FlyBase Allele Report: Dmel\vap[KS67]

General Information

Symbol

Dmel\vap^KS67

Species

D. melanogaster

Name

FlyBase ID

FBal0017844

Feature type

allele

Associated gene

Dmel\vap

Associated Insertion(s)

Carried in Construct

Also Known As

vap¹

Key Links

Allele class

amorphic allele - molecular evidence

Mutagen

ethyl methanesulfonate

Nature of the Allele

Allele class

amorphic allele - molecular evidence

(Botella et al., 2003)

Mutagen

ethyl methanesulfonate

Progenitor genotype

Cytology

Description

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)

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

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 alcohol use disorder

CEA

(Scholz et al., 2000)

Modifiers Based on Experimental Evidence ( 0 )

Disease

Interaction

References

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

adult

(Bourouis et al., 2019)

adult brain

(Wentzell et al., 2012, Botella et al., 2003, de Belle and Heisenberg, 1996)

adult optic lobe

(Botella et al., 2003)

amphisome | larval stage

(Bourouis et al., 2019)

autolysosome | larval stage

(Bourouis et al., 2019)

autophagic vacuole & neuron & adult brain

(Botella et al., 2003)

ellipsoid body

(de Belle and Heisenberg, 1996)

embryonic/larval fat body | larval stage

(Bourouis et al., 2019)

embryonic/larval fat body | larval stage | somatic clone

(Bourouis et al., 2019)

endocytic vesicle | larval stage

(Bourouis et al., 2019)

late endosome | larval stage

(Bourouis et al., 2019)

lysosome & neuron & adult brain

(Botella et al., 2003)

lysosome | larval stage | increased number

(Bourouis et al., 2019)

lysosome | second instar larval stage

(Bourouis et al., 2019)

neuron & adult brain

(Botella et al., 2003)

nodulus

(de Belle and Heisenberg, 1996)

Detailed Description

Statement

Reference

vap^KS67 adults show significantly decreased body-mass, whether raised in standard or poor diet, as compared to controls; these individuals are hypersensitive to acute food deprivation, but not if fed 15% sucrose only. The sensitivity of vap^KS67 homozygous adults to acute food deprivation is fully rescued by the expression of vap^UAS.Tag:MYC under the control of Scer\GAL4^elav.PU, even leading to resistance to food deprivation, as compared to controls.

vap^KS67 homozygous larvae show lean fat bodies; in well fed larvae there are numerous lysosomes (LysoTracker-positive puncta) and late endosomes ( Rab7:GFP ), which are rarely or not observed in controls; in starved second instar larvae, there are more numerous and significantly larger lysosomes as compared to controls. Whereas control cells show fused autolysosomes upon short starvation (1h30min), vap^KS67 mutant cells show broaden, misshaped autophagosome membranes ( GFP:Atg8a ) next to enlarged lysosomes (LysoTracker). TEM analysis confirms the loss of typical autolysosomes and their replacement by hybrid-intermediate structures with characteristics of giant amphisomes. Larval fat body cells show increased density of Rab5-positive vesicular structures in fed individuals, but not in starved individuals, as compared to controls.

In well fed animals, vap^KS67 larval fat body clones are rare and autonomously differentiate as small-sized cells; occasionally cells are found to be eliminated by apoptosis. Cells are also small under starvation conditions.

(Bourouis et al., 2019)

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 genetic interaction network for Enhancers & Suppressors

Phenotypic Class

NOT Enhanced by

Statement

Reference

vap^KS67 has decreased cell size | larval stage | somatic clone phenotype, non-enhanceable by Scer\GAL4^Act5C.PU/Atg1^JF02273

(Bourouis et al., 2019)

Suppressed by

Statement

Reference

vap^KS67 has abnormal starvation stress response | adult stage phenotype, suppressible by Atg5^RNAi.UAS/Scer\GAL4^arm.PU

(Bourouis et al., 2019)

vap^KS67 has short lived | calorie restriction conditional phenotype, suppressible by Atg5^RNAi.UAS/Scer\GAL4^arm.PU

(Bourouis et al., 2019)

vap^KS67 has abnormal starvation stress response | adult stage phenotype, suppressible | partially by Nf1^UAS.cUa/Scer\GAL4^arm.PU

(Bourouis et al., 2019)

vap^KS67 has short lived | calorie restriction conditional phenotype, suppressible | partially by Nf1^UAS.cUa/Scer\GAL4^arm.PU

(Bourouis et al., 2019)

vap^KS67 has abnormal starvation stress response | adult stage phenotype, suppressible | partially by Scer\GAL4^arm.PU/RasGAP1^UAS.cUa

(Bourouis et al., 2019)

vap^KS67 has short lived | calorie restriction conditional phenotype, suppressible | partially by Scer\GAL4^arm.PU/RasGAP1^UAS.cUa

(Bourouis et al., 2019)

vap^KS67 has abnormal neuroanatomy | adult stage phenotype, suppressible by Scer\GAL4^elav-C155/Appl^s.UAS.Tag:HA

(Wentzell et al., 2012)

NOT suppressed by

Statement

Reference

vap^KS67 has decreased cell size | somatic clone | larval stage phenotype, non-suppressible by Scer\GAL4^Act5C.PU/Atg1^JF02273

(Bourouis et al., 2019)

Other

Statement

Reference

Egfr^WT.hs, vap^KS67 has lethal phenotype

(Botella et al., 2003)

Phenotype Manifest In

NOT Enhanced by

Statement

Reference

vap^KS67 has embryonic/larval fat body | larval stage | somatic clone phenotype, non-enhanceable by Scer\GAL4^Act5C.PU/Atg1^JF02273

(Bourouis et al., 2019)

NOT suppressed by

Statement

Reference

vap^KS67 has embryonic/larval fat body | somatic clone | larval stage phenotype, non-suppressible by Scer\GAL4^Act5C.PU/Atg1^JF02273

(Bourouis et al., 2019)

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 and Rescue Data

Rescued by

vap^KS67 is rescued by vap^UAS.Tag:MYC/Scer\GAL4^arm.PU

(Bourouis et al., 2019)

vap^KS67 is rescued by vap^UAS.Tag:MYC/Scer\GAL4^Mhc.PU

(Bourouis et al., 2019)

vap^KS67 is rescued by Scer\GAL4^elav.PU/vap^UAS.Tag:MYC

(Bourouis et al., 2019)

vap^KS67 is rescued by Scer\GAL4^elav-C155/vap^UAS.Tag:MYC

(Botella et al., 2003)

Partially rescued by

vap^KS67 is partially rescued by vap^UAS.Tag:MYC/Scer\GAL4^Cg.PU

(Bourouis et al., 2019)

Comments

The sensitivity of vap^KS67 homozygous adults to acute food deprivation is fully rescued by the expression of vap^UAS.Tag:MYC under the control of Scer\GAL4^elav.PU, even leading to resistance to food deprivation, as compared to controls.

(Bourouis et al., 2019)

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)

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (2)

Reported As

Symbol Synonym

vap¹

(Bourouis et al., 2019, Wentzell et al., 2012, Botella et al., 2003, Scholz et al., 2000, de Belle and Heisenberg, 1996)

vap^KS67

Name Synonyms

Secondary FlyBase IDs

References (5)

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