Open Close
General Information
Symbol
Dmel\tim01
Species
D. melanogaster
Name
FlyBase ID
FBal0035778
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
tim0
Key Links
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Comment:

Deletion of 64bp causing a frame shift in the coding sequence. The predicted translation product contains amino acids 1 to 714, with an additional 35 residues from a new reading frame. The added amino acids are ISIFRIWWLPITSSYSFWTVRPNLVDVKPFACRST.

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

Deletion of 64bp causing a frame shift in the coding sequence. The predicted translation product contains amino acids 1 to 714 (about half the length of the wild type protein), with an additional 35 residues from a new reading frame.

Not associated with an insertion of a ry+-marked P-element.

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 ( 0 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 0 )
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

The 5-week old tim01 mutant flies subjected to ad libitum feeding (ARF) have a slower heart rate compared to controls. The reduction in arrhythmia on 12-hour daytime-restricted feeding (TRF) seen in wild type is not observed in tim01 mutant flies.

tim01 mutants exhibit normal light-dependent temperature preference. Similarly to wild-type, they prefer higher temperature in the light than in the dark.

Total sleep at nighttime and daytime is significantly decreased in tim01 mutants compared with wild-type. This is caused mainly by sleep episode duration.

Sleep bout duration and sleep latency are significantly reduced compared to controls in mutant flies.

tim01 mutant flies exhibit arrhythmic temperature preference rhythm in constant darkness after two days and in constant light at day 4. There is also a 'masking' effect of the light-dark cycle, in which tim01 flies prefer a higher temperature during the day (ZT1-12) and a lower temperature during the night (ZT13-24). tim01 flies kept in constant light for 4 days prefer a higher temperature during the daytime than flies kept in constant darkness for 2 days.

During the daytime, tim01 flies constantly prefer a temperature of approximately 26.5[o]C and do not exhibit a daytime temperature preference rhythm in light-dark conditions.

Triglyceride levels in tim01 mutants are similar to wild-type.

tim01 homozygotes exhibit aberrant locomotor rhythm under conditions of constant darkness.

tim01; timT:Avic\GFP-YFP flies do not show significant changes in period at different temperatures.

Naive and trained responses to a magnetic field are not impaired in tim01 mutant flies.

In contrast to w1118 controls, tim01 larvae show neutral performance in phototaxis tests, prefer light to darkness in the immediate light/dark boundary passing test, and demonstrate no significant motility alteration in the dark condition.

No significant difference is found in the number of dendritic branches between ZT2 and ZT14 in tim01 mutants.

16.7% of timZ2-3326/tim01 flies are arrhythmic under constant darkness conditions. The period of rhythmic mutant flies is 28.7 +/- 0.28 hours, longer than that of controls.

The rhythmic change in bouton size that is seen in motor neuron MN5 under LD (12 hour light:12 hour dark) conditions and DD (constant darkness) conditions in wild-type flies is abolished in mutant flies.

Motor neuron MN5 shows increased neuronal branching in mutant flies compared to wild type. This increased branching is associated with axonal abnormalities such as thickenings, sprouting and coiling in high-order branches.

tim01 females show a significantly higher level of ovarian diapause compared to wild-type females.

tim01 has no effect on experience-dependent responses in sleep need.

tim01 flies driven by a light:dark cycle show a steady decline in sleep:wake rhythm strength with age.

tim01 flies have poorly consolidated sleep compared with wild type flies: mutant flies have more sleep bouts and a shorter sleep bout duration. There is no substantial increase in the sleep fragmentation of tim01 flies with age: although sleep bout numbers increase somewhat with age, the average duration of sleep bouts does not increase.

tim01/+ flies show arrhythmicity when kept in constant light, like wild-type flies. tim01/tim01; timper3'UTR.tim.T:Ivir\HA1/timper3'UTR.tim.T:Ivir\HA1 flies show a low percentage (7%) rhythmicity when kep in constant light.

tim01 mutants exhibit no circadian regulation of locomotor behaviour under light-dark conditions, other than a preference for being active during the light phase.

tim01 mutant larvae are insensitive to light in light avoidance assays, even at high light intensity (750 lux). Increasing the light to 1100 lux partially rescues the photophobic defects of tim01 mutants, indicating that these mutants are not completely blind and that the molecular clock regulates visual sensitivity.

Homozygotes are arrhythmic for locomotor activity under free-running conditions.

Mutant flies are arrhythmic for locomotor activity under constant light conditions at a constant temperature of 25[o]C, but become rhythmic immediately after being exposed to a temperature cycle of 12 hours at 25[o]C and 12 hours at 30[o]C. Peaks in locomotor activity occur at temperature transitions. The locomotor activity rhythm of the mutant flies differs from that of wild-type flies, in that neither anticipatory activity nor transients after a transfer to temperature cycles is observed.

The time spent copulating is significantly increased in tim01 mutant males mated to wild-type females, compared to wild-type males. This effect is seen in both 2 day old and 4 day old males. This increased time in copulation does not appear to be due to difficulty of males disengaging from females. The time spent copulating by tim01/tim03 males mated with wild type females is significantly extended compared to wild-type.

Long term memory of courtship conditioning (reduction in time spent in courtship behaviour 5 days after a 7 hour conditioning) is normal in tim01 homozygous males.

tim01 flies are arrhythmic with respect to locomotor activity under constant darkness conditions.

Single tim01 mutant females mated once to single tim01 mutant males lay significantly less eggs and produce significantly less progeny than wild-type flies. The percentage of unfertilised eggs from this mating is significantly greater than for wild-type. These effects on fertility are significantly reduced if pairs of per01 mutant flies are allowed to mate over a period of 4 days. Single wild-type females mated once to single tim01 mutant males lay significantly less eggs and produce significantly less progeny than those mated to wild-type males. The numbers of sperm released to the seminal vesicles by tim01 males over the 2 days following eclosion is significantly less than that seen in wild-type males. Single tim01/tim03 females mated once to single tim01/tim03 males produce significantly less progeny than do wild-type flies, even though the number of eggs laid and the percentage of fertilised eggs is not significantly different to wild-type. tim01/tim03 males have significantly less sperm in their seminal vesicles 42 hours after eclosion than wild-type males.

Mutant females show altered sleep rebound after sleep deprivation of 7, 9 or 12 hours (in constant darkness) compared to wild-type flies.

tim01/tim03 flies show arrhythmic locomotor activity.

96% of tim01 flies are arrhythmic.

When wild-type flies are moved from a LD cycle to a DD cycle, at CT12 (circadian time) there is a reduction in mating activity seen. This reduction is abolished in tim01 mutants. If either male or females are mutant, this abolition of mating rhythm is seen, even if they are mated to wild-type flies.

timmutTim15/tim01 and timmutTim3/tim01 flies are almost completely arrhythmic with respect to locomotor activity.

The circadian rhythms seen in wild-type cultured malphighian tubules and rectums are essentially eliminated.

The baseline rest patterns of tim01 flies studied in constant darkness conditions are arrhythmic. After rest deprivation at circadian time (CT) 18-24, tim01 flies show a significant decrease in rest, similar to handled control wild-type flies. tim01 flies significantly decrease rest after deprivation compared to handled tim01 controls.

Homozygotes are have completely arrhythmic circadian cycles.

Heterozygotes have a locomotion period indistinguishable from wild-type flies.

Unlike other circadian gene mutants, tim01 flies show a wild-type response to cocaine exposure.

Circadian rhythms in olfactory responses to ethyl acetate or benzaldehyde are abolished in tim01 mutants.

Behaviorally arrhythmic at 18oC, 25oC and 29oC. The molecular program is stuck at about ZT 7-8.

Homozygous flies are arrhythmic with respect to locomotor activity.

Only 9% of flies are arrhythmic with respect to locomotor activity under 12 hour light:12 hour dark conditions.

Exposure of flies to constant light causes a tim01 phenocopy i.e. behavioral arrhythmia.

Individuals are arrhythmic.

Phenotype of tim01 homozygotes is indistinguishable from that of tim01/Df(2L)tim-02.

Altered eclosion rhythm, night-emerging and day-emerging adults. Defects in locomotor activity, flies become arrhythmic when the entraining light-dark cues are absent. No detectable defect in nervous system, visual system or brain.

Aberrant behavioural phenotype and localisation of per.

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

tim01 has abnormal circadian rhythm | partially phenotype, non-suppressible by perT/per[+]

NOT Suppressor of
Statement
Reference
Other
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference

timls/tim01, jetc (Veela/tim01) flies show 22% anomalous rhythmicity when kept in constant light, while flies of the same genotype that additionally carry one copy of the timper3'UTR.tim.T:Ivir\HA1 transgene (which has the same coding sequence as the timls allele) show 63% rhythmicity in constant light.

tim01;cryb double mutants and per01;tim01;cryb triple mutants do not show any locomotor anticipation of lights off at 18oC, although some residual behaviour is recovered at 29oC. tim01;cryb double mutants and per01;tim01;cryb triple mutants exhibit no change in the phase relationship of the locomotor peak to the lights off signal, as the peak activity moves progressively later as it tracks increasing length light-dark cycles.

Surprisingly, constitutive expression of both per and tim using Scer\GAL4elav-C155 restores rhythms in per01,tim01 double mutant flies.

The addition of timS1/tim01 or tim01/+ does not suppress the dcoar/dcoj3B9 and dcoar/Df(3R)tll-g arrhythmic phenotypes. the addition of perT/+ has nor effect on the arrhythmia phenotype seen in tim01 flies.

Xenogenetic Interactions
Statement
Reference

The behavioural locomotor rhythm (under constant darkness conditions) is restored in about 44.3% of tim01 flies that are expressing Dana\timhs.PN.

Complementation and Rescue Data
Comments

Under conditions of constant darkness, wild-type locomotor activity is restored in tim01; timT:Avic\GFP-YFP flies.

Under conditions of constant darkness, tim01; timT:Avic\GFP-YFP flies show abnormal locomotor activity, as in tim01 mutants. Most of these flies produce long-period (~30.5 hour) rhythms while the remainder (~30%) are arrhythmic.

The extension of time spent copulating seen in tim01/tim03 males mated with wild type females is significantly suppressed by timtim.PR.

The locomotor activity arrhythmicity of tim01/tim03 flies can be rescued by a tim rescue transgene.

The locomotor phenotype is partially rescued by timmTim4; 72% of tim01 flies carrying timmTim4 are rhythmic and the rhythmic individuals have wild-type periods. 27-40% of tim01 flies carrying timmTim1 are rhythmic, but the periods are long, ranging from 30.5 to 48 hours.

Images (0)
Mutant
Wild-type
Stocks (4)
Notes on Origin
Discoverer
Comments
Comments

Single mutation is responsible for the aberrant phenotypes.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (8)
Reported As
Symbol Synonym
tim1
Name Synonyms
timeless01
Secondary FlyBase IDs
    References (137)