FlyBase Allele Report: Dmel\tko[25t]

General Information

Symbol

Dmel\tko^25t

Species

D. melanogaster

Name

FlyBase ID

FBal0016812

Feature type

allele

Associated gene

Dmel\tko

Associated Insertion(s)

Carried in Construct

Key Links

Genomic Maps

JBrowse

Allele class

Mutagen

N-methyl-N'-nitro-N-nitrosoguanidine

Nature of the Allele

Allele class

Mutagen

N-methyl-N'-nitro-N-nitrosoguanidine

(Judd et al., 1972, Shannon et al., 1972)

Progenitor genotype

Cytology

Description

Amino acid replacement: L85H.

(Shah et al., 1997)

FlyBase curator comment: The numbering used in Figure 1 of FBrf0100242 refers to the E. coli sequence, which gives the amino acid replacement as L56H, however counting the D. melanogaster sequence shows the affected residue to be 85. Also has silent A to G substitution at a Gln residue. The affected residue lies close to one of the conserved regions implicated in translational fidelity.

(Shah et al., 1997)

Nucleotide substitution: T?C.

(Shah et al., 1997)

Nucleotide substitution: A?G.

(Shah et al., 1997)

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

X:2,442,531..2,442,531 [-]

Nucleotide change:

T2442531A

Reported nucleotide change:

T?A

Amino acid change:

L85H | tko-PB; L99H | tko-PC

Reported amino acid change:

L85H

Comment:

Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

(Shah et al., 1997)

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 sensorineural hearing loss

CEA

(Toivonen et al., 2001)

model of epilepsy

CEA

(Jacobs and Sehgal, 2020, Kemppainen et al., 2016, Whelan et al., 2010, Tan et al., 2004)

model of mitochondrial metabolism disease

CEA

(Kemppainen et al., 2014)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of mitochondrial metabolism disease

is NOT ameliorated by Cint\AOX^UAS.cFa

(Kemppainen et al., 2014)

is NOT ameliorated by Zzzz\AOX^Scer\UAS.cFa

(Kemppainen et al., 2014)

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

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal auditory perception

(Toivonen et al., 2001)

abnormal behavior

(Judd et al., 1972, Shannon et al., 1972)

abnormal behavior | recessive

(Ganetzky and Wu, 1982)

abnormal courtship behavior | male

(Chen et al., 2012, Toivonen et al., 2001)

abnormal courtship behavior | male limited

(Fernández-Ayala et al., 2010)

abnormal developmental rate

(Kemppainen et al., 2014, Chen et al., 2012, Kemppainen et al., 2009, Toivonen et al., 2003)

abnormal developmental rate (with tko³)

(Toivonen et al., 2003)

abnormal developmental rate (with tko³), with tko^25t.tTa

(Toivonen et al., 2003)

abnormal developmental rate | conditional

(Salminen et al., 2019)

abnormal developmental rate | female

(Toivonen et al., 2001)

abnormal developmental rate | male

(Toivonen et al., 2001)

abnormal mating

(Toivonen et al., 2001)

abnormal neurophysiology

(Pavlidis and Tanouye, 1995)

abnormal neurophysiology | adult stage

(Tan et al., 2004)

bang sensitive

(Kemppainen et al., 2014, Chen et al., 2012, Kemppainen et al., 2009, Tan et al., 2004, Toivonen et al., 2003, Shah et al., 1997, Engel and Wu, 1994)

bang sensitive (with tko³), with tko^25t.tTa

(Toivonen et al., 2003)

bang sensitive | recessive

(Toivonen et al., 2001)

chemical sensitive

(Toivonen et al., 2001)

decreased fecundity | female

(Fernández-Ayala et al., 2010)

lethal, with Scer\GAL4^da.PU, tko^UAS.cTa

(Toivonen et al., 2003)

lethal | cold sensitive

(Toivonen et al., 2001)

lethal | female | recessive

(Shah et al., 1997)

partially lethal - majority die (with tko³)

(Toivonen et al., 2003)

partially lethal - majority die (with tko³), with tko^25t.tTa

(Toivonen et al., 2003)

short lived (with tko³), with tko^25t.tTa

(Toivonen et al., 2003)

short lived | conditional

(Salminen et al., 2019)

viable

(Shah et al., 1997)

visible

(Judd et al., 1972, Shannon et al., 1972)

Phenotype Manifest In

macrochaeta

(Judd et al., 1972, Shannon et al., 1972)

mitochondrial chromosome | pupal stage | increased number | conditional

(Salminen et al., 2019)

mitochondrion

(Sen et al., 2013)

Detailed Description

Statement

Reference

tko^25t in the mitochondrial (cybrid) background of several Drosophila melanogaster strains (mtORT, mtWT5A and mtVAG1) leads to delays (slightly more pronounced in males) in egg to adult development; a significantly shortened life span (except males with mtWT5A); and a significantly increased number of copy of mitochondrial DNAs in late pupae when compared to controls.

(Salminen et al., 2019)

tko^25t mutants are bang sensitive and exhibit developmental delay.

(Kemppainen et al., 2014)

Mutant neuroblasts have normal mitochondrial distribution, however a proportion of the mitochondria look round and swollen.

(Sen et al., 2013)

tko^25t mutants are developmentally delayed, bang sensitive, and display male courtship defects, but these phenotypes are highly dependent on cytoplasmic background.

(Chen et al., 2012)

The total number of eggs laid by tko^25t females over 5 days is approximately half the number laid by wild-type females.

(Fernández-Ayala et al., 2010)

Rapid acute exposure to 100% CO[[2]], N[[2]] or He causes seizure-like activity in tko^25t mutants. Seizure-like activity is characterized by violent spinning of the flies accompanied by rapid uncoordinated movement of the wings, legs and abdomen. The initial bout of seizure-like activity, which usually occurs within 10 seconds of the onset of gas exposure, is followed by a period of paralysis in which the flies lay motionless. The paralysis is interrupted by bouts of delayed seizure-like activity that begins 30 to 60 seconds following the initial seizure-like activity. The delayed seizure-like activity is much more variable than the initial activity, as it often consists of multiple bouts of activity interspersed with periods of paralysis.

Only 5% of tko^25t flies are susceptible to mechanical shock 3 minutes after N[[2]] induced seizure-like activity.

Exposure of tko^25t flies to a 50/50 mix of CO[[2]] and O[[2]] results in initial and delayed seizure-like activity, indicating that hypercapnia is sufficient to trigger seizure-like activity in these flies as they have more than twice the level of atmospheric oxygen during exposure to the 50/50 mix. These flies are also susceptible to CO[[2]] induced anesthetization.

Mixtures of 95% N[[2]] and 5% O[[2]] or 95% He and 5% O[[2]] do not trigger seizure-like activity in bss¹ flies. In fact, at 98% N[[2]] or He and 2% O[[2]], these flies do not exhibit seizure-like activity, although they do become sluggish. When the amount of O[[2]] is reduced even further to 1% or less, the flies begin to become anesthetized and in many cases exhibit seizure-like activity.

Exposure of tko^25t to pure CO[[2]], He or O[[2]] for 2-5 minutes results in initial seizure-like activity but fails to generate the delayed seizure-like activity seen following acute exposure. After the initial seizure-like activity, the flies remain motionless throughout the duration of the 2- to 5-minute gas exposure. Once the gas exposure ends, the flies gradually recover normal function without displaying any delayed seizure-like activity.

(Whelan et al., 2010)

tko^25t mutant inbred lines display a developmental delay compared to controls, with eclosion delayed by 5-7 days. tko^25t mutants are bang sensitive.

(Kemppainen et al., 2009)

Mutants are bang-sensitive, with a recovery period of 42 +/- 6 seconds and a refractory period of 480 +/- 22 seconds.

Mutant flies show a reduced seizure threshold compared to wild type.

(Tan et al., 2004)

tko^25t mutant flies as well as transgenic flies carrying one or three additional copies of tko^25t mutant allele in the tko^25t background all display developmental delay and bang sensitivity phenotype of comparable severity.

tko³/tko^25t transheterozygous females are able to complete development but with an extremely long delay and majority fail to eclose successfully. The adults that manage to eclose are extremely lethargic, attempts at bang-sensitivity measurements lead to prolonged or permanent paralysis and most die shortly after eclosion.

tko³/tko^25t transheterozygotes carrying additional one or three copies of the tko^25t.tTa mutant allele on a transgene improved the phenotypic defects of the transheterozygotes: the developmental delay is reduced, greater fraction of the flies manage to eclose, the adults show long but measurable recovery times in the bang-sensitivity assay and greatly reduced adult lifespan.

(Toivonen et al., 2003)

Hemizygous males and homozygous females show a strong bang-sensitive phenotype with a mean recovery of over 30 seconds after 10 seconds of vortexing. Mean reactivity of mutant flies (measured as the distance travelled in the first minute in response to a mechanical disturbance) is less than half that of wild-type flies. Mutant flies show normal activity in a circadian rhythm machine and are rhythmic. Mutant males are rejected by wild-type females. They are moderately successful in courting mutant females, but show a substantially prolonged courtship and reduced mating time compared to wild type. Wild-type males are equally successful at courting either mutant or wild-type females. Mutant males show only a very slight response to courtship song at 100dB, whereas wild-type males show a clear response at 70-90dB, suggesting a hearing defect in mutant males. Mutant flies take approximately 2-3 days longer to develop at 25^oC than wild-type flies. This effect is more marked in males than in females; mean developmental delay to eclosion is 2.40 +/- 0.10 days in mutant males and 2.17 +/- 0.006 days in mutant females. The developmental delay occurs almost exclusively during the larval stages, mostly during the second and third instars. There is no delay during embryogenesis and there is no maternal effect on developmental timing. Mutant flies show temperature sensitivity; survival to eclosion at 21^oC is 86% of wild type, while at 16^oC survival is only 19% of wild type. Mutant flies are hypersensitive to doxycylin, showing reduced survival to eclosion compared to wild type and an extended developmental delay when raised in the presence of doxycylin. Streptomycin has no significant effect on the development of mutant (or wild-type) flies.

(Toivonen et al., 2001)

Female hemizygotes are lethal.

(Shah et al., 1997)

Bang-sensitive mutant. Flies usually show abnormal spontaneous activity ("seizures") in the dorsal longitudinal muscle (DLM) lasting approximately 0.5-3 seconds after the delivery of an electrical buzz (50-400 msec) to the brain. Stimulation of the giant fibre (GF) usually fails to evoke DLM potentials following the buzz. This failure lasts for 54 +/- 14 seconds. There is a close correlation between the seizure and failure phenotypes; if a seizure occurs, a failure also occurs in greater than 95% of cases, while failures without seizures occurred in approximately 10% of cases. GF evoked responses by the DLM are abnormal during recovery from the buzz. After recovery, there is a refactory period during which a buzz is less effective at inducing seizures and failures.

(Pavlidis and Tanouye, 1995)

Physiological defect: a striking reduction of spike frequency in the anterior post-alar (APA) and anterior notopleural (ANP) after mechanical stimulus.

(Engel and Wu, 1994)

Bang sensitive paralytic mutant.

(Ganetzky and Wu, 1982)

Homozygous males and females are semi-lethal. Survivors exhibit a fine bristle phenotype and are sensitive to shock.

(Judd et al., 1972)

Semilethal, surviving males and homozygous females have short thin bristles and are highly sensitive to physical shock.

(Shannon et al., 1972)

quasi-viable and behaviorally defective; female hemizygotes lethal

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

NOT Enhanced by

Statement

Reference

tko^25t has abnormal behavior phenotype, non-enhanceable by Df(2L)TW1/+

(Fergestad et al., 2006)

Suppressed by

Statement

Reference

tko^25t has abnormal developmental rate phenotype, suppressible | partially by Scer\GAL4^da.G32/srl^UAS.cTa

(Chen et al., 2012)

tko^25t has bang sensitive phenotype, suppressible | partially by Scer\GAL4^da.G32/srl^UAS.cTa

(Chen et al., 2012)

tko^25t.tTa, tko^25t has abnormal developmental rate phenotype, suppressible by mRpL14^{GreenH-Pelican}

(Kemppainen et al., 2009)

tko^25t.tTa, tko^25t has bang sensitive phenotype, suppressible by mRpL14^{GreenH-Pelican}

(Kemppainen et al., 2009)

tko^25t has abnormal developmental rate phenotype, suppressible by Dp(1;1)weeb¹

(Kemppainen et al., 2009)

tko^25t has bang sensitive phenotype, suppressible by Dp(1;1)weeb¹

(Kemppainen et al., 2009)

tko^25t has abnormal developmental rate phenotype, suppressible by Dp(1;1)weeb²

(Kemppainen et al., 2009)

tko^25t has bang sensitive phenotype, suppressible by Dp(1;1)weeb²

(Kemppainen et al., 2009)

tko^25t has abnormal developmental rate phenotype, suppressible by Dp(1;1)weeb³

(Kemppainen et al., 2009)

tko^25t has bang sensitive phenotype, suppressible by Dp(1;1)weeb³

(Kemppainen et al., 2009)

tko^25t has abnormal developmental rate phenotype, suppressible by mRpL14^{GreenH-Pelican}

(Kemppainen et al., 2009)

tko^25t has bang sensitive phenotype, suppressible by mRpL14^{GreenH-Pelican}

(Kemppainen et al., 2009)

NOT suppressed by

Statement

Reference

tko^25t has bang sensitive phenotype, non-suppressible by Cint\AOX^UAS.cFa/Scer\GAL4^βTub.Switch

(Kemppainen et al., 2014)

tko^25t has abnormal behavior phenotype, non-suppressible by Df(2L)TW1/+

(Fergestad et al., 2006)

Other

Statement

Reference

mt:Cyt-b^KSA2, tko^25t has visible | third instar larval stage phenotype

(Salminen et al., 2019)

mt:Cyt-b^KSA2, tko^25t has melanotic necrosis | pharate adult stage phenotype

(Salminen et al., 2019)

mt:Cyt-b^KSA2, tko^25t has melanotic necrosis | pupal stage phenotype

(Salminen et al., 2019)

mt:Cyt-b^KSA2, tko^25t has melanotic necrosis | third instar larval stage phenotype

(Salminen et al., 2019)

mt:Cyt-b^KSA2, tko^25t has visible | pupal stage phenotype

(Salminen et al., 2019)

mt:Cyt-b^KSA2, tko^25t has increased cell number | third instar larval stage phenotype

(Salminen et al., 2019)

mt:Cyt-b^KSA2, tko^25t has lethal - all die before end of P-stage phenotype

(Salminen et al., 2019)

Scer\GAL4^da.G32, Scer\NDI1^UAS.cSa, tko[+]/tko^25t has partially lethal phenotype

(Kemppainen et al., 2014)

Scer\GAL4^da.G32, Scer\NDI1^UAS.cSa, tko^25t has partially lethal - majority die phenotype

(Kemppainen et al., 2014)

Cint\AOX^UAS.cFa, Scer\GAL4^da.G32, Scer\NDI1^UAS.cSa, tko[+]/tko^25t has partially lethal phenotype

(Kemppainen et al., 2014)

Cint\AOX^UAS.cFa, Scer\GAL4^da.G32, Scer\NDI1^UAS.cSa, tko^25t has lethal - all die before end of P-stage phenotype

(Kemppainen et al., 2014)

Phenotype Manifest In

Other

Statement

Reference

mt:Cyt-b^KSA2, tko^25t has mitochondrial chromosome | increased number | pupal stage phenotype

(Salminen et al., 2019)

mt:Cyt-b^KSA2, tko^25t has embryonic/larval hemocyte | increased number | third instar larval stage phenotype

(Salminen et al., 2019)

Additional Comments

Genetic Interactions

Statement

Reference

tko^25t in the mitochondrial (cybrid) background of Drosophila melanogaster strain (mt:Cyt-b^KSA2) leads to a significantly increased number of larval hemocytes; third instar larval, pupal and pharate adult melanotic nodules; and a significantly increased copy number of mitochondrial DNA in late pupae when compared to controls.

(Salminen et al., 2019)

Expression of srl^Scer\UAS.cTa under the control of Scer\GAL4^da.G32 partially rescues the developmental delay and bang sensitivity phenotypes of tko^25t mutants.

(Chen et al., 2012)

A Dp(1)weeb¹ background completely suppresses the developmental delay found in tko^25t mutants. These flies exhibit almost wild-type developmental timing and are no longer bang sensitive. The ratio of 12S:16S mitochondrial rRNAs, which represents a marker for the relative amount of small and large mito-ribosomal subunits, and is diagnostic for the mutant phenotype, is found to be intermediate between that seen in outbred tko^25t flies and in wild-type flies.

A Dp(1)weeb² background completely suppresses the developmental delay found in tko^25t mutants. These flies exhibit almost wild-type developmental timing and are no longer bang sensitive. The ratio of 12S:16S mitochondrial rRNAs, which represents a marker for the relative amount of small and large mito-ribosomal subunits, and is diagnostic for the mutant phenotype, is found to be intermediate between that seen in outbred tko^25t flies and in wild-type flies.

A Dp(1)weeb³ background completely suppresses the developmental delay found in tko^25t mutants. These flies exhibit almost wild-type developmental timing and are no longer bang sensitive. The ratio of 12S:16S mitochondrial rRNAs, which represents a marker for the relative amount of small and large mito-ribosomal subunits, and is diagnostic for the mutant phenotype, is found to be intermediate between that seen in outbred tko^25t flies and in wild-type flies.

The presence of mRpL14^{GreenH-Pelican} fails to suppress the developmental delay found in tko^25t mutants.

A combination of mRpL14^{GreenH-Pelican} and tko^25t.tTa fails to rescue bang sensitivity or the delay in eclosion seen in tko^25t mutants.

(Kemppainen et al., 2009)

Df(2L)TW1/+ does not significantly alter the seizure phenotype of tko^25t hemizygotes.

(Fergestad et al., 2006)

Xenogenetic Interactions

Statement

Reference

Expression of Zzzz\AOX^Scer\UAS.cFa under the control of Scer\GAL4^βTub.Switch, in combination with RU486 feeding in either larval stages or adulthood, is unable to rescue the bang sensitivity or developmental delay of tko^25t mutants.

Expression of Scer\NDI1^Scer\UAS.cSa under the control of Scer\GAL4^da.G32 in tko^25t/tko^25t mutants results in nearly complete lethality, and in tko^25t/+ mutants results in partial lethality.

Co-expression of Zzzz\AOX^Scer\UAS.cFa and Scer\NDI1^Scer\UAS.cSa under the control of Scer\GAL4^da.G32 in tko^25t/tko^25t mutants results in complete lethality, and in tko^25t/+ mutants results in partial lethality.

(Kemppainen et al., 2014)

Complementation and Rescue Data

Rescued by

tko^25t is rescued by tko^25t-H85L.tTa

(Toivonen et al., 2001)

Not rescued by

tko^25t is not rescued by tko^25t.tTa

(Kemppainen et al., 2009)

tko^25t is not rescued by tko^25t.tTa

(Toivonen et al., 2001)

Comments

Ectopic copies of tko^25t.tTa fails to rescue bang sensitivity in tko^25t mutants and only a minimal rescue of developmental delay.

(Kemppainen et al., 2009)

Images (0)

Mutant

Wild-type

Stocks (1)

Bloomington

93885

tko^25t/FM7a

Notes on Origin

Discoverer

Comments

No apparent defect in the larval neuromuscular junction preparation. Behavioral phenotype suppressed by mle^nap-ts1, even at permissive temperatures.

(Ganetzky and Wu, 1982)

External Crossreferences and Linkouts ( 1 )

Crossreferences

GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.

AJ250320

Synonyms and Secondary IDs (2)

Reported As

Symbol Synonym

tko(25t)

(Shah et al., 1997)

tko^25t

(Cuddapah et al., 2025, Jacobs and Sehgal, 2020, Radlicz et al., 2019, Salminen et al., 2019, Kemppainen et al., 2016, Kemppainen et al., 2014, Vartiainen et al., 2014, Sen et al., 2013, Chen et al., 2012, Fernández-Ayala et al., 2010, Whelan et al., 2010, Kemppainen et al., 2009, Toivonen et al., 2007, Fergestad et al., 2006, Tan et al., 2004, Toivonen et al., 2003)

Name Synonyms

Secondary FlyBase IDs

References (26)

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