Open Close
General Information
Symbol
Dmel\Tpisgk-1
Species
D. melanogaster
Name
sugarkill
FlyBase ID
FBal0241671
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
TPIsugarkill, TPIsgk
Mutagen
    Nature of the Allele
    Mutagen
    Mutations Mapped to the Genome
     
    Type
    Location
    Additional Notes
    References
    point mutation
    Nucleotide change:
    T30133805C
    Reported nucleotide change:
    T?C
    Amino acid change:
    M182T | Tpi-PA; M81T | Tpi-PB; M81T | Tpi-PC
    Reported amino acid change:
    M80T
    Associated Sequence Data
    DNA sequence
    Protein sequence
     
     
    Progenitor genotype
    Cytology
    Nature of the lesion
    Statement
    Reference
    A missense mutation that affects an amino acid that exists at the dimer interface of the expressed protein.
    Amino acid replacement: M80T.
    Nucleotide substitution: T?C.
    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
    Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
     
    The neurological phenotypes of the Tpisgk-1 allele (which can be used to model triosephosphate isomerase deficiency) are genetically complemented by an allele (TpiK11M) which encodes a catalytically inactive enzyme. This suggests a non-metabolic function for Tpi in D.melanogaster, the loss of which contributes significantly to the neurological defects in the Tpisgk-1 animal model.
    Phenotypic Data
    Phenotypic Class
    Phenotype Manifest In
    Detailed Description
    Statement
    Reference
    Ratios of redox molecules are significantly shifted towards the oxidised form in homozygous and Tpisgk-1/Tpisgk-js10 animals compared to controls. This phenotype is age-dependent. Mitochondria in homozygous flies are oxidatively stressed, even at a young age. Homozygous flies show a "bang sensitive" phenotype and show paralysis at high temperature. Both phenotypes are significantly worsened by treatment with hydrogen peroxide and is significantly improved by treatment with sub-lethal levels of beta-mercaptoethanol. Homozygous flies are hypersensitive to hydrogen-peroxide mediated oxidative stress and resistant to high doses of beta-mercaptoethanol compared to controls.
    Tpisgk-1/TpiWT flies show no sign of paralysis or seizures upon mechanical stress. Tpisgk-1 homozygotes and Tpisgk-1/Tpisgk-js10 flies show a delay in recovery after mechanical stress compared to controls, at both 3 and 20 days of age. Tpisgk-1 homozygotes and Tpisgk-1/Tpisgk-js10 flies show paralysis upon thermal stress, at both 3 and 20 days of age. Tpisgk-1 homozygotes and Tpisgk-1/Tpisgk-js10 flies show significantly reduced median longevity compared to controls.
    The mechanical stress sensitivity of mutant animals is significantly improved if the animals are treated with MG132 or Geldanamycin.
    Mutants show a bang sensitive phenotype at both room temperature and at 29[o]C, taking longer to recover from mechanical stress than control flies.
    Tpisgk-1/Tpisgk-js10 flies take longer to regain normal locomotion after mechanical stress than control flies. This stress sensitivity is progressive and increases significantly with the age of the flies at all temperatures examined (room temperature, 25oC and 29oC). Severe stress sensitivity is evident much earlier in flies maintained at 25oC or 29oC compared to those raised at room temperature. Lifespan of homozygous and Tpisgk-1/Tpisgk-js10 animals is significantly reduced compared to controls at room temperature, 25oC and 29oC. The decrease in lifespan compared to controls becomes more severe as the temperature at which the flies are raised is increased. Young Tpisgk-1/Tpisgk-js10 adults do not show neuropathological defects, however, by their median age, they develop marked neuropathology, showing degeneration in the brain and thoracic ganglion. This degeneration is seen in flies raised at room temperature, 25oC and 29oC. Mitochondria in the brain and the indirect flight muscle appear normal in homozygous adults.
    External Data
    Interactions
    Show genetic interaction network for Enhancers & Suppressors
    Phenotypic Class
    Phenotype Manifest In
    Additional Comments
    Genetic Interactions
    Statement
    Reference
    The mechanical stress sensitivity of Tpisgk-1 animals is significantly suppressed if they are also mutant for Hsp8308445 or Hsp83e6A. The mechanical stress sensitivity of Tpisgk-1 animals is significantly suppressed if they are also expressing Hsc70-4K71S.Scer\UAS under the control of Scer\GAL4Act5C.Switch.PR (in the presence of Mifepristone). The mechanical stress sensitivity of Tpisgk-1 animals is enhanced if they are also expressing Hsc70-4Scer\UAS.cEa under the control of Scer\GAL4Act5C.Switch.PR (in the presence of Mifepristone).
    Pros261/+ can partially suppress the reduced median lifespan of Tpisgk-1 homozygous flies when the double mutants are raised at 29[o]C.
    Xenogenetic Interactions
    Statement
    Reference
    Complementation and Rescue Data
    Fails to complement
    Comments
    TpiK11M fully complements the mechanical and thermal stress sensitive phenotypes of Tpisgk-1, at both 3 days and 20 days after eclosion. TpiK11M also complements the reduced longevity phenotype of Tpisgk-1. TpiK11M fails to complement the markedly reduced isomerase activity seen in Tpisgk-1.
    Images (0)
    Mutant
    Wild-type
    Stocks (0)
    Notes on Origin
    Discoverer
    Comments
    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (10)
    Reported As
    Name Synonyms
    Secondary FlyBase IDs
    • FBal0138457
    • FBal0194554
    References (8)