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General Information
Symbol
Dmel\trpP365
Species
D. melanogaster
Name
FlyBase ID
FBal0102369
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
Trp365
Key Links
Allele class
Mutagen
    Nature of the Allele
    Allele class
    Mutagen
    Mutations Mapped to the Genome
     
    Type
    Location
    Additional Notes
    References
    Nucleotide change:

    C29917594A

    Amino acid change:

    H531N | trp-PA

    Reported amino acid change:

    H531N

    Comment:

    One of four lesions associated with this allele; site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

    Nucleotide change:

    C29917687A

    Amino acid change:

    P500T | trp-PA

    Reported amino acid change:

    P500T

    Comment:

    One of four lesions associated with this allele; site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

    Nucleotide change:

    T29917537A

    Amino acid change:

    F550I | trp-PA

    Reported amino acid change:

    F550I

    Comment:

    One of four lesions associated with this allele; site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

    Nucleotide change:

    C29915943T

    Amino acid change:

    S867F | trp-PA

    Reported amino acid change:

    S867F

    Comment:

    One of four lesions associated with this allele; site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

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

    Amino acid replacement: P500T. Amino acid replacement: H531N. Amino acid replacement: F550I. Amino acid replacement: S867F. The mutations P500T and H531N immediately flank the fourth transmembrane segment S4 and F550I is within the fifth transmembrane segment.

    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 ( 1 )
    Disease
    Interaction
    References
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Disease-implicated variant(s)
     
    Phenotypic Data
    Phenotypic Class
    Phenotype Manifest In
    Detailed Description
    Statement
    Reference

    Young trpP365/+ flies have normal eye morphology whereas aged flies show rapid degeneration with condensed cytoplasm, vesicle accumulation and rhabdomere loss (no difference compared to controls at day 1, with a significant decrease in the number of rhabdomeres per ommatidium at day 3, 5 and 8). Photoreceptors from trpP365/+ 3 and 5 day old flies contain morphologically abnormal (larger and more vacuolated compared to controls) mitochondria (phenotype is more severe at 5 days old); mitochondrial function is also significantly affected.

    Heterozygous photoreceptors appear normal at eclosion, but show degeneration over time.

    Homozygous 1 to 2 day old flies elicit essentially no electroretinogram response to light stimulus. Heterozygous flies 1 to 2 day old flies elicit an electroretinogram response to light stimulus that is approximately half way between that of homozygous and wild-type flies.

    The average resting potential of heterozygous photoreceptors is significantly smaller than that of wild type.

    The eyes of trpP365 mutants show loss of rhabdomeres, disorganization of ommatidia, and vacuolarization throughout the retina and photoreceptors.

    Homozygous flies show severe rhabdomere degeneration.

    trpP365/+ flies show almost complete retinal degeneration after being reared in the dark for 10 days.

    trpP365 flies on day 0 post-eclosion exhibit normal rhabdomere organisation. However, by day 6 post-eclosion, all flies exhibit errors in rhabdomere organisation or integrity.

    trpP365 heterozygotes exhibit all seven rhabdomeres at day 0 post-eclosion, but no intact rhabdomeres by 8 days post eclosion.

    trpP365/+ flies exhibit significantly reduced ERGs with markedly slower termination kinetics at stimulation off and nearly or completely absent on-transients. Very small transients re sometimes present in young trpP365/+ flies, but these disappear by day 7 post-eclosion. R1-R6 photoreceptors are almost completely non-functional in these mutants.

    Heterozygotes and homozygotes have defective electroretinograms. The rhabdomeres of some ommatidia begin to show abnormalities by day 3 after eclosion in heterozygous flies. By day 7, most rhabdomeres are no longer structurally intact and most ommatidia no longer have a full complement of 7 rhabdomeres. Only a few isolated rhabdomeres are detectable even at day 0 post-eclosion in homozygous flies.

    Homozygotes have very little electroretinogram (ERG) responses remaining. Heterozygotes have an ERG response intermediate between that of wild-type and trpP365 homozygotes, i.e. the phenotype is semi-dominant. The mutant ERG phenotype is present at eclosion in heterozygotes and gradually deteriorates further with age. The small responses seen in trpP365/trpP365, trpP365/trp9 or trpP365/trp1 flies are not "transient" but have a maintained component that persists throughout the duration of the stimulus. No deep pseudopupil is detected at eclosion in homozygous flies, regardless of whether the flies have been raised in complete darkness or 12 hour light/dark cycles. The deep pseudopupil is intact in all newly eclosed heterozygous flies but disappears in a progressively larger fraction of flies as they age. The deep pseudopupil disappears with a t1/2 of approximately 1.5 days in 12 hour light/dark illumination cycles, whereas it disappears with a t1/2 of approximately 4.5 days when the flies are raised in complete darkness. The photoreceptors of homozygotes are severely degenerated 0 days after eclosion, so that no recognisable rhabdomeres can be seen in cross sections of the retina from relatively proximal levels. The photoreceptors appear quite normal even at 2 days after eclosion in heterozygotes raised in complete darkness. In 2 day old heterozygotes raised in 12 hour light/dark cycles, however, photoreceptors begin to show evidence of degeneration. One or more rhabdomeres are missing in many ommatidia and some photoreceptors are degenerating. The photoreceptors of homozygotes (either pupae or less than 1 hour old adults) show no response to light of any intensity (as measured by whole-cell recordings of light-induced currents - LICs). The LIC of heterozygotes (either pupae or less than 1 hour old adults) is indistinguishable from wild type. In the case of trpP365/trp1 animals raised at 19oC and examined at the P15 pupal stage, a large subset of photoreceptors respond to light with smaller than normal responses. The remaining subset (43%) do not respond to light at all. In less than 1 hour old trpP365/trp1 adults, 93% of photoreceptor cells do not respond to light. trpP365/trpP365 and trpP365/trp1 photoreceptors (in darkness) respond to voltage steps with large outward currents and significant inward currents. The properties of these currents are very similar to those of the run down current of wild-type photoreceptors, except that they are seen from the moment the recordings begin and in a normal medium. Newly eclosed trpP365/trp1 flies show virtually no signs of photoreceptor degeneration when raised at 19oC. Several hours later, the photoreceptor cells begin showing membrane shedding at the tips of some microvilli, suggesting that degeneration has begun.

    Causes very rapid degeneration of the photoreceptor cells. No deep pseudopupil (dpp) is detectable upon eclosion in homozygotes. In heterozygotes the dpp disappears within 2-3 days after eclosion.

    External Data
    Interactions
    Show genetic interaction network for Enhancers & Suppressors
    Phenotypic Class
    Enhanced by
    Suppressed by
    NOT suppressed by
    Phenotype Manifest In
    Enhanced by
    Suppressed by
    Statement
    Reference

    trpP365 has retina phenotype, suppressible by su(rdgA)4040

    trpP365 has rhabdomere phenotype, suppressible by su(rdgA)4040

    trpP365 has retina phenotype, suppressible by CalxninaE.PW

    trpP365 has photoreceptor cell phenotype, suppressible by Df(1)inaF-P106x/+

    NOT suppressed by
    Additional Comments
    Genetic Interactions
    Statement
    Reference

    Expression of CalxScer\UAS.cMa or SERCAScer\UAS.T:Hsap\MYC driven by Scer\GAL4GMR.PF suppresses retinal degeneration (loss of rhabdomeres from photoreceptors) in 5 day old trpP365/+ flies. Expression of Letm1Scer\UAS.cHa driven by Scer\GAL4GMR.PF enhances retinal degeneration (loss of rhabdomeres from photoreceptors) in 5 day old trpP365/+ flies.

    Expression of Atg1Scer\UAS.cSa driven by Scer\GAL4GMR.PF (to induce autophagy) partially suppresses age-dependent retinal degeneration (loss of rhabdomeres from photoreceptors) and restores mitochondrial morphology in trpP365/+ flies. Co-expression of Tsc1Scer\UAS.cGa and gigScer\UAS.cTa driven by Scer\GAL4GMR.PF (to induce autophagy) partially suppresses age-dependent retinal degeneration (loss of rhabdomeres from photoreceptors) in trpP365/+ flies.

    Pink1B9 or park1/park1 suppresses the ability of Scer\GAL4GMR.PF>Atg1Scer\UAS.cSa to suppress age-dependent retinal degeneration (loss of rhabdomeres from photoreceptors) in trpP365/+ flies. Expression of Pink1Scer\UAS.T:Ivir\HA1 or parkScer\UAS.T:Zzzz\FLAG driven by Scer\GAL4GMR.PF does not suppress age-dependent retinal degeneration (loss of rhabdomeres from photoreceptors) in trpP365/+ flies; co-expression of both Pink1Scer\UAS.T:Ivir\HA1 and parkScer\UAS.T:Zzzz\FLAG results in significant partial suppression of the phenotype.

    Expression of Opa1Scer\UAS.T:Zzzz\FLAG (positive regulator of mitofusion) driven by Scer\GAL4GMR.PF enhances retinal degeneration (loss of rhabdomeres from photoreceptors) in 8 day old trpP365/+ flies. Expression of Drp1Scer\UAS.cDa (positive regulator of mitofission) or TER94Scer\UAS.cHb driven by Scer\GAL4GMR.PF suppresses retinal degeneration (loss of rhabdomeres from photoreceptors) in 8 day old trpP365/+ flies.

    su(rdgA)4040 suppresses the retinal degeneration seen in trpP365/+ flies.

    The electroretinogram phenotype of trpP365 heterozygotes is enhanced by inaEN125, such that the resulting electroretinogram phenotype resembles that of trpP365 homozygotes.

    The electroretinogram phenotype of trpP365 heterozygotes is enhanced by inaEN125/inaEKG08585 and by inaEKG08585/inaEKG08585.

    The number of rhabdomeres per ommatidium is significantly rescued in trpP365 flies by expression of either NmnatScer\UAS.cZa or NmnatWR.Scer\UAS under the control of Scer\GAL4GMR.PF. However, the vacuolarization that occurs in trpP365 retinae and photoreceptors is not suppressed by either transgene.

    The retinal degeneration phenotype of trpP365 flies is not rescued by inaDsu100 or inaDsu1, but is rescued by su(rdgA)4040.

    The retinal degeneration seen in trpP365/+ flies reared in the dark for 10 days is almost completely suppressed by expression of CalxninaE.PW.

    The trpP365 photoreceptor cell degeneration phenotype is suppressed by Df(1)inaF-P106x. Degeneration is slower in Df(1)inaF-P106x, trpP365/+ than in either single mutant.

    Xenogenetic Interactions
    Statement
    Reference
    Complementation and Rescue Data
    Rescued by
    Partially rescued by

    trpP365 is partially rescued by trp+t6.4

    Comments

    The presence of trpdsRNA.PG in a trpP365 heterozygous background rescues rhabdomere organisation and integrity at least up to 28 days post-eclosion. Photoreceptor degeneration is completely rescued through expression of trpdsRNA.PG, as are ERG amplitudes. R1-R6 photoreceptors, which are pereviously non-functional, are now functional and contribute to the near normal ERG amplitudes and to the generation of the transients. However, the termination time course of the responses at stimulus offset was still slower than in wild-type, indicating that rescue is not complete.

    The electroretinogram (ERG) phenotype of trpP365/+ heterozygotes is substantially rescued by one copy of trp+t6.4, and is almost completely rescued by two copies of trp+t6.4 (the return to baseline after stimulus offset is slightly slower than normal). The ERG phenotype of trpP365 homozygotes is rescued to an ERG approaching that of trpP365/+ heterozygotes in size by two copies of trp+t6.4.

    Images (0)
    Mutant
    Wild-type
    Stocks (1)
    Notes on Origin
    Discoverer
    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (5)
    References (14)