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General Information
Symbol
Dmel\Ras85DV12.cUa.UAS
Species
D. melanogaster
Name
FlyBase ID
FBal0276789
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-RasV12, UAS-RasV12, RasV12, UAS-Ras85DV12
Key Links
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Nucleotide change:

G9512257T

Amino acid change:

G12V | Ras85D-PA

Comment:

Analogous to oncogenic mutations in one of three human RAS genes; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator based on reported amino acid change.

Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Carried in construct
Cytology
Nature of the lesion
Statement
Reference

UAS regulatory sequences drive expression of a V12 mutant of Ras85D.

Allele components
Product class / Tool use(s)
Encoded product / tool
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 )
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
model of  cancer
is exacerbated by M6W186stop
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

The tumor invasion model is generated by expression of Ras85DV12.cUa.UAS in combination with the l(2)gl4 mutation within eye disc clones.

Disease-implicated variant(s)
 
This allele represents a human variant implicated in disease.

This somatic variant has been found associated with cancer in each of the three paralogous genes in human (KRAS, HRAS, NRAS).

HRAS:p.Gly12Val
Variants Synonym(s)
Associated human disease model(s)
External database links
Comments concerning this variant
KRAS:p.Gly12Val
Variants Synonym(s)
Associated human disease model(s)
External database links
Comments concerning this variant
NRAS:p.Gly12Val
Variants Synonym(s)
Associated human disease model(s)
External database links
Comments concerning this variant
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Whole-eye disc clones expressing Ras85DV12.cUa.UAS alone under the control of Scer\GAL4Act5C.PP do not form tumors.

The expression of DlUAS.cDa under the control of Scer\GAL4ey.PH induces an increase in eye size, with a high frequency of tumors.

The expression for one week during adulthood of Ras85DV12.cUa.UAS under the combined control of Scer\GAL4byn-Gal4 and Gal80[ts] (for the temporal control of expression) results in significant increases in apoptosis and senescence in the hindgut, in dissemination of hindgut cells to distant body areas, and in a severe increase in actively replicating cells (i.e. BrU-positive) in the pylorus, but does not affect the amount of food intake by adults, as compared to controls.

Somatic clones expressing Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4Act.PU in wandering third instar wing discs present a significant increase in relative clonal area, as compared to control clones.

The constitutive expression of Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4ap.PU leads to larval lethality and to the overgrowth, but not to the generation of mesenchymal-like cells, of third instar larval wing discs as compared to controls. The constitutive expression under the control of Scer\GAL4GMR.PU leads to pupal lethality, but not to any cell migration defect in the pupal eye tissue, as compared to controls.

Expression of Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4ptc.PU in cells of the wing disc proper has no significant effect on the morphology or proliferation of the overlying peripodial membrane cells in third instar larvae.

trametinib treatment at 15.6uM doubles the lifespan of flies expressing Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4da.Switch.PT.

Adult Scer\GAL4tin.CΔ4>Ras85DV12.cUa.Scer\UAS flies have smaller heart chambers with reduced end-diastolic dimensions compared with controls. Histological analysis of cardiac chambers from adult transgenic flies show heart wall thicknesses that are two to three times compared with controls. Hearts isolated from the transgenic flies show abnormal cardiac morphology with myofiber disarray compared with controls. The number of cells in the transgenic hearts is similar to that in wild-type, indicating that the increased wall thickness is the result of cardiomyocyte hypertrophy, not an increase in cell proliferation.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference
NOT Enhanced by
Suppressed by
Statement
Reference
NOT suppressed by
Enhancer of
NOT Enhancer of
Suppressor of
NOT Suppressor of
Other
Statement
Reference
Phenotype Manifest In
Enhanced by
Statement
Reference
NOT Enhanced by
Suppressed by
Statement
Reference
NOT suppressed by
Enhancer of
NOT Enhancer of
Suppressor of
NOT Suppressor of
Other
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference

Co-expressing PtendsRNA.Exel.UAS and Ras85DV12.cUa.UAS under the control of Scer\GAL4repo.PU induces larval central brain gliomas; brain lobes are enlarged; there is an increase in mitosis; there is an increase in the number of neuroblasts; neuroblasts and ganglion mother cells seem to undergo a lateral shift at the edge of the central brain abutting the optic lobe.

Expression of Ras85DV12.cUa.UAS under the control of Scer\GAL4spok.1.45 in the Kdm5140 homozygous background leads to curved-down wings compared to controls.

Whole-eye disc clones both l(2)gl4 homozygous and expressing Ras85DV12.cUa.UAS under the control of Scer\GAL4Act5C.PP form tumors that invade into the VNC; the VNC invasion phenotype is nearly suppressed by the co-expression of pucUAS.cUa, partially suppressed by the co-expression of licJF01433 and partially suppressed by licG0252 heterozygosity; however, the size of the primary tumor is not affected by these manipulations.

Likewise, whole-eye disc clones co-expressing Ras85DV12.cUa.UAS and licUAS.ORF under the control of Scer\GAL4Act5C.PP frequently form tumors that invade into the VNC.

Quadruple or quintuple co-expression for one week during adulthood of Ras85DV12.cUa.UAS, p53VDRC.cUa, PtenGD13500, ApcVDRC.cUa and/or MedVDRC.cUa under the combined control of Scer\GAL4byn-Gal4, Dicer-2 (for efficient RNAi) and Gal80[ts] (for the temporal control of expression) leads to multilayered epithelia that form bulges at discrete points along the hindgut (only in animals that contained Ras85DV12.cUa.UAS and ApcVDRC.cUa together) and to an expanded pylorus (observed in the quintuple and all quadruple conditions that carried Ras85DV12.cUa.UAS); the quadruple co-expression conditions Ras85DV12.cUa.UAS+p53VDRC.cUa+PtenGD13500+MedVDRC.cUa and p53VDRC.cUa+PtenGD13500+ApcVDRC.cUa+MedVDRC.cUa do not lead to multilayering.

All quadruple and quintuple co-expression conditions - with the exception of the quadruple p53VDRC.cUa+PtenGD13500+MedVDRC.cUa+ApcVDRC.cUa - result in numerous hindgut cells losing their characteristic epithelial shape to assume a more mesenchymal appearance (processes extending towards the basement membrane and surrounding muscle layer), migrate locally and disseminate to distant sites in the organism (e.g. head, legs, fat body, ovaries, below the epidermis of the abdomen and within the abdominal cavity). Similar hindgut cell dissemination is observed upon the triple expressions of Ras85DV12.cUa.UAS+p53VDRC.cUa+PtenGD13500, Ras85DV12.cUa.UAS+ApcVDRC.cUa+PtenGD13500 or Ras85DV12.cUa.UAS+p53VDRC.cUa+ApcVDRC.cUa, the double expressions of Ras85DV12.cUa.UAS+p53VDRC.cUa, Ras85DV12.cUa.UAS+PtenGD13500 or Ras85DV12.cUa.UAS+ApcVDRC.cUa, all of which are more severe than upon the single expression of Ras85DV12.cUa.UAS alone.

Somatic clones co-expressing wupAf06492 and Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4Act.PU in wandering third instar larval wing discs present a significant increase in the relative clonal area as compared to clones only expressing Ras85DV12.cUa.Scer\UAS, but not to clones only expressing wupAf06492, and lead to overgrowths protruding from the wing disc in almost half of cases.

The induction of somatic clones co-expressing l(2)glGD4047 and Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4Act.PU during second instar larval stage results in the accumulation of clonal cells in the wandering third instar larval fat body, which is enhanced by the additional co-expression of wupAJF02172; the induction of these clones also results in lethality before adulthood, which is partially rescued by the additional co-expression of wupAJF02172, although the surviving adults display a shorter life-span as compared to wild-type controls.

In wandering third instar larvae, somatic clones co-expressing l(2)glGD4047 and Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4Act.PU in both eye discs and wing discs exhibit a significant increase in the relative clonal area and hyperplasia as compared to control clones; wing disc clone cells localize both basally and apically in the disc. All of these phenotypes are suppressed by the additional co-expression of wupAJF02172, even leading to a significant decrease in the wing disc clonal area as compared to control clones.

Somatic clones co-expressing l(2)glGD4047, Ras85DV12.cUa.Scer\UAS and wupAf06492 under the control of Scer\GAL4Act.PU in wandering third instar larvae wing discs exhibit a significant increase in relative clonal area as compared to clones only co-expressing l(2)glGD4047 and Ras85DV12.cUa.Scer\UAS or only expressing wupAf06492; animals bearing clones co-expressing l(2)glGD4047, Ras85DV12.cUa.Scer\UAS and wupAf06492 do not reach adulthood.

Co-expression of Ras85DV12.cUa.Scer\UAS increases the extent of migration into the posterior compartment of anterior cells expressing Vha44Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4ptc-559.1 in the wing disc.

Co-expression of Ras85DV12.cUa.Scer\UAS enhances the wing pouch overgrowth caused by expression of Vha44Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4nub.PU.

Xenogenetic Interactions
Statement
Reference

Whole-eye disc clones co-expressing Ras85DV12.cUa.UAS and Hsap\MAP2K3UAS.cSa under the control of Scer\GAL4Act5C.PP frequently form tumors that invade into the VNC.

The triple co-expression of Ras85DV12.cUa.Scer\UAS, Hsap\UBE3AScer\UAS.cRa and either HPV18\E6Scer\UAS.T:Hsap\MYC or HPV18\E6V158A.Scer\UAS.T:Hsap\MYC, under the control of Scer\GAL4GMR.PU, leads to the migration of a considerable proportion of expressing eye tissue cells into distant pupal tissues (e.g. abdomen), as compared to controls. The triple co-expression of Ras85DV12.cUa.Scer\UAS, Hsap\UBE3AScer\UAS.cRa and HPV18\E6V158A.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4GMR.PU does not suppress the pupal lethality induced by the single expression of Ras85DV12.cUa.Scer\UAS under the control of Scer\GAL4GMR.PU.

Co-expression of Ras85DV12.cUa.Scer\UAS with Zzzz\aopPScer\UAS.T:Hsap\MYC under the control of Scer\GAL4GMR.PF does not alter the eye morphology of Zzzz\aopPScer\UAS.T:Hsap\MYC-expressing eyes.

Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (4)
Reported As
Symbol Synonym
Ras85DV12.cUa.Scer\UAS
Ras85DV12.cUa.UAS
Name Synonyms
Secondary FlyBase IDs
    References (27)