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General Information
Symbol
Dmel\mad2G6595
Species
D. melanogaster
Name
FlyBase ID
FBal0277486
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
mad2P
Allele class
Mutagen
    Nature of the Allele
    Allele class
    Mutagen
    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

    The P{EP}mad2G6595 P-element is inserted at nucleotide 389 of mad2, at the beginning of exon 3.

    Insertion components
    P{EP}mad2G6595
    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 )
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Disease
    Interaction
    References
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Phenotypic Data
    Phenotypic Class
    Phenotype Manifest In
    Detailed Description
    Statement
    Reference

    mad2G6595 homozygous third instar larval brains do not display obvious defects in volume, overall tissue organization (including layer size and organization, size and organization of medullar axons, and numbers of neuroblasts and neuroepithelial cells), proportions of apoptotic cells (assessed by Hid-GFP, cleaved Casp-3 and cleaved Dcp-1), mitotic cells and DNA-damaged cells, and frequency of ploidy defects and progression time to anaphase in central brain neuroblasts, as compared to controls.

    The number of neuroblasts in mad2G6595 mutant larval brains is not significantly different from wild-type controls and the brain tissue lacks the ability to induce tumor formation in an tissue allograft assay.

    Unlike wild-type controls, mad2G6595-derived syncitial-stage embryos fail to undergo mitotic arrest in response to spindle damage induced by colchicine-treatment.

    Most of the polar bodies in embryos laid by mad2G6595 mutant mothers are large with semi- or fully decondensed chromatin.

    Mitosis 14 anaphase appears largely normal in mad2G6595 mutant embryos.

    mad2G6595 mutant larvae develop at slightly faster rate than wild type flies.

    mad2G6595 mutants do not show accumulation of mitotic cells in colchicine-treated larval brains.

    mad2G6595 mutant colchicine-treated larval brains exhibit a significant increase in aneuploid cells.

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

    mad2G6595, Sas-4s2214 double homozygotes exhibit a developmental delay, until arresting and dying at the larval\pupal transition, as compared to controls. Their third instar larval, but not second instar larval or embryonic, brains display a severe decrease in overall volume, a severe increase in the proportion of apoptotic cells (assessed by Hid-GFP, cleaved Casp-3 and Dcp-1), a severe increase in the overall mitotic index (including of the central brain neuroblast population), and a significant increase in the proportion of DNA damaged cells, as compared to controls. Third instar larval brains also display severe tissue organization defects, which mostly affect the optic lobes, as compared to controls: loss or strong reduction of the medulla layer, which exhibits very few neuroblasts and decreased numbers of disorganized neuroepithelial cells; apparent loss of the lamina layer; decreased size of the medullar neuropil, associated with decreased size and disorganization of the axons from medullar neurons; decreased size and complexity of the outer optic anlagen (but not at the second instar larval stage); decreases in number and in organization of central brain neuroblasts, which are able to divide symmetrically, but occasionally exhibit an increased cell size and differentiation defects (i.e. expressing both Dpn and Pros proteins); but not any obvious defects in the mushroom body. Homozygosity for mad2G6595 strongly enhances the frequency of ploidy defects, but not the delayed entry into anaphase, observed in Sas-4s2214-homozygous third instar larval central brain neuroblasts.

    mad2G6595, aslmecD and mad2G6595, cnnHK21 double homozygous third instar larval brains display a strong decrease in volume, as compared to single mutants and wild-type controls.

    The increased number of brain neuroblast (NB) cells characteristic for aurA8839 mutant third instar larvae is slightly elevated further by combination with homozygous mad2G6595, whereas the increased mitotic index, the highly condensed chromosome appearance in mitotic cells and the tumorigenic potential of the double mutant tissue in an allograft assay are not significantly affected compared to aurA8839 single mutant. The delay in the timing of mitotic cell cycle events is ameliorated in aurA8839;mad2G6595 brain NBs compared to aurA8839 cells but not wild-type level, no lagging chromatids (indicative of incorrect spindle attachment) are observed during anaphase and telophase.

    aurA8839;Sas-4s2214;mad2G6595 triple mutants show high rate of ploidy defects in third instar larval brains, the number of neuroblasts or the mitotic cells is highly increased relative to wild-type but significantly different from aurA8839;Sas-4s2214 double mutants.

    The increased brain neuroblast (NB) number observed in Sas-4s2214 mutant third instar larvae is fully suppressed by combination with mad2G6595 (the NB number in the double mutants is even lower than in wild-type controls and the brains are also smaller), while the NB mitotic spindle defects are enhanced and numerous aneuploid or polyploid cells are frequently observed. The double mutant brain tissue also cannot (unlike that from Sas-4s2214 single mutants) induce tumor formation in an allograft assay.

    The presence of a TEV protease cleavable form of vtd (by expressing vtd271TEV.tub.T:Zzzz\TEV.CS,T:Hsap\MYC and Zzzz\NIaScer\UAS.T:SV5\V5,T:SV40\nls2 in a vtdex3 mutant background) suppresses the chromosome segregation defects seen in embryos expressing aldScer\UAS.cAa under the control of Scer\GAL4mat.αTub67C.T:Hsim\VP16 in a mad2G6595 mutant background. This suppression does not occur in the absence of Zzzz\NIaScer\UAS.T:SV5\V5,T:SV40\nls2.

    Injection of geminin into mad2G6595 embryos abolishes the mitotic delay observed when geminin is injected into wild type embryos.

    BubR1A1204K.PR-mad2G6595 double mutants are not delayed in prometaphase (as in BubR1A1204K.PR single mutants) but instead show a rapid mitotic transit time and early onset of CycB degradation (as in mad2G6595 single mutants). Double mutants are uniformly larval/pupal lethal and double mutant brains exhibit a lower mitotic density with neuroblast aneuploidy and abnormal anaphases more frequent than in both single mutants.

    BubR1KEN.T:Disc\RFP-mRFP mad2G6595 double mutants are viable and fertile, with aneuploidy levels no higher than in the single mutants. Anaphase figures also appear normal in double mutants. The time from nuclear envelope breakdown to anaphase is markedly reduced (by 40%) compared to BubR1KEN.T:Disc\RFP-mRFP single mutant or wild-type cells and 30% reduced compared to mad2G6595 single mutants. This acceleration is accompanied by an earlier onset of CycB breakdown. In contrast, the gap from CycB breakdown to anaphase is relatively constant between the double mutant and controls.

    mad2G6595 cnnHK21 double mutants exhibit a shortened prometaphase with an increase in aneuploidy compared to both single mutants and are larval lethal.

    Homozygous mad2G6595 suppresses the developmental rate defects seen in larvae expressing SAKUbi.T:Avic\GFP, producing instead a slight increase in the rate of development as is seen in mad2G6595 mutants alone. The mitotic index in mad2G6595 SAKUbi.T:Avic\GFP brains is lower than in either wild type or SAKUbi.T:Avic\GFP expressing neuroblasts. The number of multipolar and defective spindles is dramatically increased compared to flies expressing SAKUbi.T:Avic\GFP and polyploidy, aneuploidy and lagging chromosomes are all seen during anaphase. The number of centrosomes per cell is increased compared to SAKUbi.T:Avic\GFP.

    mad2G6595 rev7 double mutants (where the rev7 mutant is constructed as noi+t3.6; noiA/Df(3R)noi-B) are viable and show no greater aneuploidy than mad2G6595 single mutants.

    mad2G6595 cnnHK21 double mutants exhibit a severely delayed spindle assembly pathway, resulting in a higher mitotic index and a broad peak anaphase onset time of 8-16 minutes. Larval brains of mad2G6595 cnnHK21 double mutants have a very high incidence of polyploidy and mad2G6595 cnnHK21 individuals die as early pupae.

    Xenogenetic Interactions
    Statement
    Reference

    The decreased brain volume of mad2G6595, Sas-4s2214 double homozygous third instar larvae is partially suppressed by the expression of BacA\p35Scer\UAS.cHa under the control of Scer\GAL4insc-Mz1407.

    Complementation and Rescue Data
    Comments
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    Mutant
    Wild-type
    Stocks (0)
    Notes on Origin
    Discoverer
    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (3)
    Reported As
    Name Synonyms
    Secondary FlyBase IDs
    • FBal0244141
    • FBal0243504
    References (10)