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General Information
Symbol
Dmel\per01
Species
D. melanogaster
Name
FlyBase ID
FBal0013649
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
per0, perO1, pero, per01
Key Links
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Nucleotide change:

C2689758T

Reported nucleotide change:

C?T

Amino acid change:

Q464term | per-PA; Q464term | per-PB

Reported amino acid change:

Q464term

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

Stop codon within the per locus.

Nucleotide substitution: C?T.

Amino acid replacement: Q464term.

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 ( 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

per01 adults exhibit arrhythmic locomotor behavior in DD and arrhythmic feeding behavior in both LD (light-dark cycle) and DD when compared to controls.

perper-STOP.dmpi8UP/per01 flies are arrhythmic in constant dark conditions.

per01/Y mutant adults have significantly reduced strength of circadian locomotor rhythms under constant darkness, compared to heterozygous controls.

per01/per01 mutants exhibit significantly higher sensitivity to alcohol sedation when exposed to 50% ethanol vapor, and a significant increase in time to recovery from alcohol-induced sedation, as compared to wild type; and these mutants also do not exhibit any circadian rhythm-dependent changes in the time to alcohol sedation, or in time to recovery from alcohol-induced sedation, in contrast to wild type.

per01/per01 mutant flies do not exhibit a significant change in locomotor activity or period of sustained rest, as compared to wild type.

Transgenic per8:8 flies in a per01 mutant genetic background exhibit sleep patterns very similar to those previously described for wild-type strains, including the temperature and gender differences on daytime sleep.

Transgenic perM2M1 flies in a per01 mutant genetic background exhibit sleep patterns that are different to those previously described for wild-type strains at 18[o]C and 25[o]. While daytime sleep is reduced compared with wild-type, nighttime sleep appears normal. The transgenic mutant flies also sleep less during the nighttime in the presence of light at 18[o]C and 25[o]. However, at the elevated temperature of 29[o]C, daytime sleep is similar for transgenic mutant and wild-type flies, and high temperature strongly inhibits daytime activity in both perM2M1 , per01 transgenic mutants and wild-type.

per01 mutant adults have a significantly lower circadian clock entrainment index for locomotor activity rhythms following a 7 h delay under 25[o] C:27 [o]C temperature cycles under constant light conditions, compared to controls.

The heart period in 5-week old per01 mutant flies subjected to ad libitum feeding (ARF) is similar to controls. The heart period does not change on 12-hour daytime-restricted feeding (TRF). The reduction in arrhythmia on TRF seen in wild type is smaller in per01 mutant flies.

per01 mutants exhibit normal light-dependent temperature preference. Similarly to wild-type, they prefer higher temperature in the light than in the dark.

Adult per01 flies expressing perS826A.S828A.T:Ivir\HA1,T:Zzzz\His6 (rescue flies) display robust circadian locomotor activity rhythm in constant dark (preceded by an 12:12 light:dark entrainment period) with a period of ~23 hr - about 1 hr shorter than wild-type, the upswing in the morning activity peak occurs earlier compared to controls but the timing of the evening activity bout is not significantly affected. When entrained on a short photoperiod regime ( 9:15 light:dark cycle), the timing of both evening and morning peaks is early, substantially so (by ~1.4 hr) for the morning one. The per01;perS826A.S828A.T:Ivir\HA1,T:Zzzz\His6 flies also show defects in the temperature compensation of period length: their free-running locomotor activity periods shorten with the rising temperature. However, neither the cycling pattern of per mRNA expression nor the timing of the per protein nuclear entry is perturbed in these mutants and they also do not display any defects in photic entrainment abilities.

Adult per01 flies expressing any of the following: perΔ.T:Ivir\HA1,T:Zzzz\His6, perS828D.T:Ivir\HA1,T:Zzzz\His6 or perS826D.T:Ivir\HA1,T:Zzzz\His6 (rescue flies) display robust circadian activity rhythm in constant dark (preceded by an 12:12 light:dark entrainment period) with a period of around 24 hr, similarly to wild-type. Flies expressing either perS826A.T:Ivir\HA1,T:Zzzz\His6 or perS828A.T:Ivir\HA1,T:Zzzz\His6 display period significantly shorter than wild-type ~23 hr.

The per01;perS826D.S828D.T:Ivir\HA1,T:Zzzz\His6 flies show defects in temperature compensation of period length: their free-running locomotor activity periods lengthen with the rising temperature.

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

Unlike wild-type, the vast majority of per01 mutant adults show a distinct ultradian rhythmicity in walking activity under constant dark conditions, with a mean ultradian period of about 90min.

Homozygous per01 mutants display arrhythmia in free-running conditions.

Compared with wild-type, perT610A.S613A.S1187A.T:Ivir\HA1,T:Zzzz\His6 expression leads to a dramatic increase in period length (~30 hour) in per01 genetic background.

Compared with wild-type, perT610A.S613A.T:Ivir\HA1,T:Zzzz\His6 expression leads to a dramatic increase in period length in per01 genetic background.

Compared with wild-type, perS613A.T:Ivir\HA1,T:Zzzz\His6 expression leads to increased period length in per01 genetic background.

1 day memory retention is impaired after spaced training, but not after massed training in an olfactory conditioning assay.

per01 mutants exhibit disruption of the daily temperature preference rhythm under constant darkness or constant light conditions. A weak rhythm appears to be present in constant light by day 4, but the preferred temperatures in each time zone are not statistically different from ZT1-3. After 2 days of constant darkness, per01 flies exhibit constant low temperature preference, except at ZT22-24. There is also a 'masking' effect of the light-dark cycle, in which per01 flies prefer a higher temperature during the day (ZT1-12) and a lower temperature during the night (ZT13-24). per01 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, per01 flies constantly prefer a temperature of approximately 26[o]C and do not exhibit daytime temperature preference rhythm in light-dark conditions.

per01 mutants exhibit complete loss of circadian rhythms, but do not display any significant difference in life span as compared to controls, do not show marked evidence of neurodegeneration as measured by presence of vacuoles in the brain, and do not exhibit any significant difference in climbing ability as compared to controls.

Triglyceride levels in per01 mutants are similar to wild-type.

Flies expressing perS661A.13.2.T:Ivir\HA1,T:Zzzz\His6 in a per01 mutant background exhibit free-running periods that are approximately 2 h longer compared with controls.

Flies expressing perS661D.13.2.T:Ivir\HA1,T:Zzzz\His6 in a per01 mutant background exhibit free-running periods that are approximately 2 h longer compared with controls.

Flies expressing perS657A.13.2.T:Ivir\HA1,T:Zzzz\His6 in a per01 mutant background exhibit free-running periods that are approximately 1 h longer compared with controls.

per01 flies tested under a 12 hours 29[o]C/12 hours 20[o]C thermal cycle in constant darkness show a temperature-driven "midday" peak of activity.

per01 mutants show no increase in sleep after social enrichment. per01 mutants have no long-term memory when tested 48 hours after training and only show a transient increase in sleep.

Under normal laboratory conditions, the longevity of per01 males is similar to wild-type controls. However, lifespan is significantly reduced in per01 flies exposed to 24 h hyperoxia in middle age. Hyperoxia on day 20 shortens the average lifespan in per01 mutants by 12% while hyperoxia on day 35 decreases average lifespan of per01 flies by 20% compared to wild-type males. Survival curves are significantly different in both ages . Mortality hazard is significantly increased after exposure to 24 h hyperoxia on day 20 or 35 in per01 mutants, but remains unchanged in wild-type males. Compared to wild-type controls, per01 mutants accumulate more oxidative damage in response to stress and during normal aging as measured by the levels of protein carbonyls and lipid peroxidation products.

Aging per01 mutants show greater mobility impairment and neurodegeneration than wild-type controls.

In LD conditions, perM560D.T:Ivir\HA1, per01 flies or perM560D.T:Hsap\MYC, per01 flies behave similarly to the controls overall, although behavioural anticipation of the D to L and L to D transitions is less pronounced. In DD conditions, only 30-60% of mutant flies are rhythmic and periods are slightly longer than controls, indicating that the circadian clock is impaired in these flies; however temperature compensation is normal.

perR345E.T:Ivir\HA1, perR345E.T:Hsap\MYC, perW482E.T:Ivir\HA1, perW482E.T:Hsap\MYC, perW482E.M560D.T:Ivir\HA1 or perW482E.M560D.T:Hsap\MYC do not restore rhythmic behaviour to per01 flies in LD or DD conditions in more than 20% of flies. The few rhythmic flies exhibit widely variable periods, and temperature compensation is severely compromised.

per01 flies lack the clear organisation of locomotor activity into morning and evening peaks under 12:12 hour light-dark conditions and under 12:12 hour light moonlight conditions (under these conditions, a dim light of quarter-moonlight intensity, 0.03 lux, is switched on during the dark phase) that is seen in wild-type flies. per01 flies show arrhythmicity for locomotor activity under constant darkness or constant moonlight conditions (wild-type flies show robust rhythmicity under these conditions).

No significant difference is found in the number of dendritic branches between ZT2 and ZT14 in per01 mutants.

Compared to wild-type controls, per01 mutant flies exhibit higher mortality after exposure to oxidative stress with no apparent rhythm in light-day cycles. In contrast to wild-type controls, per01 mutants do not show daily rhythms in the accumulation of protein carbonyls and mitochondrial hydrogen peroxide production.

The pronounced circadian rhythm of close-proximity encounters seen in wild-type male:female pairs is lost when the male is hemizygous for per01.

Flies are completely arrhythmic for locomotor activity under constant darkness conditions when raised at 25 or 29[o]C. At 18[o]C, only 6% of flies are rhythmic under constant darkness conditions (compared to 44% of wild-type controls).

Under 12 hour light: 12 hour dark conditions, flies show a "startle" response at lights-on, but there is no anticipatory rise in activity before either light or dark transitions.

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 decreased neuronal branching in mutant flies compared to wild type.

per01 mutants exhibit no circadian regulation of locomotor behaviour under light-dark conditions, other than a preference for being active during the light phase. In per01, there is 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. Hence cryb suppresses the effect of per01 on circadian activity.

per01 flies fail to entrain to a 12 hour:12 hour 25oC:18oC temperature cycle in LL but merely show a rapid, temporally restricted increase in locomotor activity during the temperature shift. Further, the flies fail to entrain to two consecutive warm:cold cycles in LL where the second cycle is phase advanced by 6 hours, instead they abruptly change their activity level at the time of temperature transition.

Expression of either the perS151A.tG, perS149A.tG, perS153.tG, perS151-153D.tG or perS149-151-153A.tG mutated genomic fragment in a per01 background results in a rescue of locomotor rhythmicity compared to per01 flies, but results in activity periods which are ~2 hours longer than per01 flies resued with a wild-type per genomic fragment.

per01 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 per01 mutants, indicating that these mutants are not completely blind and that the molecular clock regulates visual sensitivity.

per01 larvae entrained in LD cycles for 2-3 days and then shifted into DD, that are tested for their ability to avoid light at 3hr intervals on the second day of DD do not show a detectable rhythm, appearing constitutively insensitive.

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. The locomotor activity is rather concentrated during the cryophase, with a peak at early cryophase. 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 for per01 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.

Unlike wild-type males, per01 homozygous males that have undergone courtship conditioning (kept in the presence of a female for 7 or 9 hours) do not spend significantly less time engaged in courtship behaviour when placed with a female 5 days after conditioning than non-conditioned males of the same genotype. This phenotype is unaffected if the 7 hour conditioning is performed during nighttime (Zeitgeber time, 12-19). However, 11 hours courtship conditioning is sufficient to reduce courtship behaviour 5 days later in these flies. Courtship conditioning of 30 minutes is also sufficient to significantly reduce courtship behaviour 1 hour after conditioning in per01/per01 males.

Flies mutant for per01 expressing perScer\UAS.cYa under the control of Scer\GAL4elav-C155 and repressed by Scer\GAL80Pdf.PS in Pdf expressing cells, become gradually arrhythmic under DD conditions. These flies however, manifest a wild-type-like anticipation of lights-on as well as lights off peak in LD.

Single per01 mutant females mated once to single per01 mutant males lay significantly less eggs and produce significantly less progeny than wild-type flies. The percentage of unfertilised eggs from this mating is not 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 per01 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 per01 males over the 2 days following eclosion is significantly less than that seen in wild-type males.

Most per01 flies are rhythmic in LD, while most are arrhythmic in DD.

The "anticipatory" response normally seen prior to the light-to-dark transition in the locomotor activity rhythms of wild-type flies is not seen in per01 mutant flies exposed to 12 hour light:12 hour dark ( 12:12LD ) conditions. The startle response to lights-on is still seen in the locomotor activity rhythm of the mutant flies. Under constant darkness conditions, per01 flies show roughly equal amounts of locomotor activity during the subjective day and night.

Mutant females show a more prominent sleep rebound after sleep deprivation (in constant darkness) than wild-type flies; they recover 100% of lost sleep within 12 hours (wild-type flies recover 30-40% of lost sleep within 12 hours).

Mutant flies show no rhythmic locomotor activity in constant darkness.

Mutant flies remain almost continuously active as long as the lights are on in a locomotor activity assay. Most mutant flies show a prominent locomotor activity peak before lights-on under light-dark conditions. Like wild-type flies, a few mutant flies lack the morning peak completely, and thus start to be active exactly at lights on, especially under shorter Zeitgeber periods. Under longer Zeitgeber periods, the majority of mutant flies are clearly active before lights-on under light-dark conditions. The mutant morning peaks occur significantly earlier than that of wild-type flies under light-dark conditions. Mutant flies become immediately arrhythmic under constant darkness conditions in a locomotor activity assay. 72.7% of flies kept under constant darkness conditions for 2-3 weeks after being entrained for 5 days to a 12:12 light-dark cycle are completely arrhythmic. The remaining 27.3% show significant circadian periods with low power and a short period. The mutant flies show ultradian rhythms.

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 per01 mutants.

per01 flies display only transient peaks of locomotor activity under cycling conditions. These peaks are coincident with the light/dark transitions and showed no anticipatory or sustained nature.

Decapitated per01 flies show significant modulation of quinpirole-induced locomotion when kept in LD conditions, however with a lower peak-to-trough amplitude than wild-type flies. In contrast, when the quinpirole challenge is performed on per01 kept in LL, this modulation disappears. When per01 flies are kept under LD conditions, modulation of the quinpirole sensitive dopamine receptors persists without the brain input, showing that the bodies of per01 flies are photosensitive.

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

The baseline rest patterns of per01 flies studied in constant darkness conditions are arrhythmic. After rest deprivation at circadian time (CT) 18-24, per01 flies show an increase in rest that persists into the third postdeprivation day, similar to the rest rebound of wild-type flies.

In the absence of a circadian rest-activity rhythm, per01 flies show a robust homeostatic response after 12 hours of rest deprivation.

Like wildtype, per01 flies show a dose-dependent increase in behavioural responses to cocaine exposure, but unlike wild-type, per01 flies do not sensitize to repeated exposures. Unlike wild-type, per01 show no increased locomotory response to the dopamine D2-like agonist quinpirole, after exposure to cocaine. Feeding per01 flies with tyramine, increases initial behavioural responsiveness to cocaine exposure, but does not restore sensitization.

The pericardial cells of the per01 pupal heart are shrunken and wrinkled compared to wild-type flies in which they are firm and have a smooth surface.

Rhythmic locomotor activity is rescued in an average of 77.8% of per01 flies carrying perCRS.hs. Rhythmic locomotor activity is rescued in an average of 86% of per01 flies carrying perCRS.P\T.

Circadian rhythms in olfactory responses to ethyl acetate are abolished in per01 mutants. Circadian rhythms in olfactory responses to ethyl acetate are abolished in per01 mutants that also have the P{perC7.2} transgene.

Flies are behaviourally arrhythmic when locomotor activity is measured under constant darkness conditions.

The period of the interpulse interval (IPI) of the male courtship song is 31.1 seconds (wild-type value is 67.9 seconds).

Flies are arrhythmic when tested for free-running activity rhythms in constant darkness (after entraining to 12 hour light:12 hour dark cycles for 3 days).

Homozygous flies are arrhythmic with respect to locomotor activity.

Homozygous flies are diurnal at 25oC, and are rather nocturnal at 30oC under 12 hour light:12 hour dark conditions. The highest peak of activity occurs at lights-off independent of temperature. Flies are arrhythmic under constant darkness at both 25oC and 30oC.

per01; perBG.T:Ecol\lacZ flies are arrhythmic, perBG.T:Ecol\lacZ is unable to provide substantial per gene biological activity.

Abolish circadian rhythms.

Mutation has no effect on larval heartbeat.

No observable rhythmicity of eclosion or locomotor activity.

No larvae exhibit appreciable diel rhythms under cycling conditions of light or temperature. Larvae are also not rhythmic under free-running conditions.

Mutants display short circadian rhythm and males produce short song rhythms. This genetic coupling found in males does not extend to females, females have a preference for wild type courtship song over the mutant short song rhythm.

Normal grooming behavior.

Lacks normal wild type rhythmicity.

Arhythmic.

Flies are arrhythmic in constant darkness.

Arrhythmic mutant, shorter period than wild type.

per01 and per04 adults have very low melatonin and hydroxy indole O-methyl transferase levels. 5-HT, N-acetyl serotonin and N-acetyl transferase levels were in the normal range.

Measures of acquisition at intermediate and maximum levels and of 30 min memory retention are normal. Mean Courtship Index (CI) for males exposed to fertilised females for 30 mins does not differ significantly from control males with no courtship experience. After 30 mins exposure of an immature male to another immature male a significantly suppressed response to another immature male is observed. P{per13.2} transgenic flies are almost always rhythmic with near normal periodicities, in P{per14.6} transgenic flies the resulting circadian periodicity is longer than in normal flies.

Arrhythmic mutant.

Pupal and larval stages are erratically lengthened or shortened depending on the rearing conditions.

Spectral analysis of tone pulse production demonstrated that pers male courtship song is not strongly rhythmic. Arrhythmic songs are associated with cryptic rhythmicities, these period values define very short song cycle durations.

per01 larvae develop more slowly than wild-type larvae under constant bright light or under 12 hour light:12 hour dark conditions, and per01 larvae develop faster than wild-type larvae under constant very bright light. per01 flies eclose significantly faster than wild-type flies under constant darkness, constant bright light or constant very bright light, and eclose significantly more slowly than wild-type flies under 12 hour light:12 hour dark conditions.

Flies are not strictly arrhythmic, but appear to have fast cycles in their activity patterns (Hamblen-Coyle, J. Neurogenet 5: 229). Flies can be entrained to a 24 hour cycle of light and dark (Konopka, PhD Thesis, Pasadena). The effect on circadian behaviour is matched by the effect on the song cycle, a weak 20-30 sec lovesong cycle (Kyriacou and Hall, Anim Behav 37:850 ). Males do not show defective courtship conditioning (Jackson, J. Comp. Phys. A 151: 545). Transplantation of donor pers brains into per01 abdomens causes some per01 hosts to take on the donors locomotor activity characteristics (Handler, Nature 279: 236). Pericardial cells are abnormal (Livingstone, Neurosci Adstr 8: 384), these cells secrete octopamine so are perhaps responsible for the irregular heartbeat. Introduction of the perΔTG13.2 or perΔTG8.0 construct into the per01 genome caused little change to the circadian cycle, but the song cycle was shortened to a 40 second period (Yu, Nature 326:765 ). Introduction of the P{ per::Dsim \perTGs} construct into per01 gives song rhythms with a simulans-like period, short 35 to 40 second song cycles.

Arrhythmic eclosion of flies.

Normal song pulses and hums.

Arrhythmic.

Flies are arrhythmic, with no circadian or ultradian rhythms. per01 flies carrying two copies of per+t13.2 are rhythmic. Two copies of Dpse\perper.P can partially rescue per01 flies in 30% of cases.

Introduction of the perΔTG13.2 or perΔTG8.0 construct into per01 flies has little or no effect on the circadian phenotype but the courtship song rhythm periods are 30% shorter.

Brains from mutant flies, when incubated with tritiated tyrosine, accumulated one-third as much labelled octopamine as did brains from wild-type flies, but had normal dopamine and serotonin synthesis. Mutant brains show reduced activity of Tdc gene product, but normal Tbh, Ddc and 5-HTdc protein activity. Effect is indirect, perhaps by affecting octopaminergic neurons. Mutant flies have normal learning and memory.

per01/T(1;4)JC43 and per01/Ts(1Lt;4Lt)JC43+Ts(1Rt;2Rt)RC45 flies have a variable phenotype, ranging from very long-period rhythmicity, rhythms that grade into arrhythmicity, or a completely arrhythmic phenotype.

multiple periods; short ultradian rhythms

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
Suppressor of
Statement
Reference
NOT Suppressor of
Statement
Reference
Other
Phenotype Manifest In
Suppressed by
Statement
Reference

per01 has phenotype, suppressible by Dyak\perper.MY1

per01 has phenotype, suppressible by Mdoa\perper.MM1

per01 has phenotype, suppressible by Aper\perper.PL

Enhancer of
Statement
Reference

per01 is an enhancer of vacuole phenotype of sws1

per01 is an enhancer of adult brain phenotype of sws1

per01 is an enhancer of vacuole | adult stage | progressive phenotype of sni1

per01 is an enhancer of adult brain | progressive phenotype of sni1

NOT Enhancer of
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference

The presence of per01/per01 does not significantly change the elevation in locomotor activity seen in DATfmn mutants.

A per01 heterozygous background rescues the circardian arrhythmia phenotype found upon expression of p38bScer\UAS.cAa under the control of Scer\GAL4cry.PZ.

A per01 heterozygous background does not greatly affect the tau or arrhythmicity seen upon expression of p38bDD.Scer\UAS.

A per01 heterozygous background enhances the arrhythmicity and tau phenotype found upon expression of p38bala.Scer\UAS under the control of Scer\GAL4cry.PZ.

A per01 heterozygous background enhances the arrhythmicity and tau phenotype found upon expression of p38bkd.Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4cry.PZ.

per01, sws1 double mutants at 14 days old show marked increase in neurodegeneration as measured by area and number of vacuoles in the brain as compared to sws1 single mutants.

A subset of per01, sws1 double mutants exhibit some rhythmicity (13% of flies), in contrast to per01 single mutants in which 0% of flies have circadian rhythm, and sws1 single mutants in which 97% of flies have circadian rhythm.

sni1, per01 double mutants exhibit significant reduction in lifespan compared to single mutants reared in 12h light, 12h dark cycles; exhibit an increase in the neurodegeneration phenotype of sni1 single mutants with increased numbers of and area of vacuoles; and exhibit loss of circadian rhythms similar to that of per01 single mutants. Climbing performance is significantly reduced in sni1, per01 double mutants as compared to sni1 single mutants.

Expression of cycScer\UAS.T:Hsim\VP16 under the control of Scer\GAL4elav-C155 in a per01, perScer\UAS.cYa background only shortens the circadian locomotor activity period by 20 minutes, in contrast to the shortening of 2 hours seen when cycScer\UAS.T:Hsim\VP16 is expressed under the control of Scer\GAL4elav-C155 in a wild-type background.

Homozygous cwoPB9 flies with one copy of per01 show more severe lengthening of the circadian cycle than homozygous cwoPB9 alone.

The length of the circadian cycle was increased compared to wild type when perScer\UAS.cBa is expressed in homozygous cwoPB9 flies with one copy of per01 under the control of either a Scer\GAL4tim.PE or a Scer\GAL4cry.PE driver.

In contrast to wild-type animals, per01; ; cryb double mutants expressing Scer\GAL80Pdf.PS and Scer\GAL4Mai179 or Scer\GAL4cry.PE driven perScer\UAS.cBa display robust locomotor activity rhythms, with a long 25.7h period under constant light conditions.

per01; cryb double mutants exhibit a functional clock with a well-defined evening activity peak anticipating `lights off' that is absent in per01 mutants. The evening peak in activity also arrives earlier during the light phase than the wild-type, possibly suggesting an underlying short-period oscillation. per01;tim01;cryb triple mutants do not show any locomotor anticipation of lights off at 18oC, although some residual behaviour is recovered at 29oC. 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. Under constant darkness or constant light, the rhythmicity of per01;cryb breaks down during the first day. In per01;cryb mutants, brief light pulses administered at 18oC during the night phase at ZT15 and ZT21 in light-dark 12:12 cycles give advances in the phase of locomotor activity. Thus the `clock' of these flies `remembers' a previously administered light pulse, even in light-dark cycles.

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

Xenogenetic Interactions
Statement
Reference

Expression of Hsap\APP1-40.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU in a per01 mutant background does not significantly shorten lifespan compared to controls. Climbing ability is also unaffected.

Expression of Hsap\APP1-42.Scer\UAS.T:SS-nec under the control of Scer\GAL4elav.PU in a per01 mutant background does not significantly shorten lifespan compared to controls.

per01 enhances the climbing defects seen when Hsap\APP1-42.Scer\UAS.T:SS-nec is expressed under the control of Scer\GAL4elav.PU, but only in younger (5 day old) flies. No effect is seen at 15, 35 and 50 days.

per01 does not enhance the climbing defects seen when Hsap\APPArctic.Scer\UAS.T:SS-nec is expressed under the control of Scer\GAL4elav.PU.

per01 does not further enhance the increase in vacuole number seen when Hsap\APPArctic.Scer\UAS.T:SS-nec is expressed under the control of Scer\GAL4elav.PU.

per01 mutant files co-expressing perScer\UAS.cBa and Ctet\TeTxLCTNT.Scer\UAS under the control of Scer\GAL4Mai179 display morning anticipation in their locomotor activity, but they completely lose evening anticipation, compared with controls with Ctet\TeTxLCIMPTNT-V.Scer\UAS expression.

Anticipatory activity is absent in the morning and almost completely lost in the evening in per01 mutants co-expressing perScer\UAS.cBa and Ctet\TeTxLCTNT.Scer\UAS under the control of both Scer\GAL4Mai179 and Scer\GAL80Pdf.PS.

For flies kept in total darkness, the peak locomotor activity occurs at the same point in circadian time in per01/per01; 2xDpse\perper.PT D.melanogaster as in D.pseudoobscura.pseudoobscura. The overall shape of the locomotor activity curve over circadian time for these transgenic D.melanogaster is similar (but not identical) to that for D.pseudoobscura.pseudoobscura.

Mmus\Per1tim.PS shows some rescue of the per01 phenotype; 5.4% of the rescued flies show locomotor activity rhythms in constant darkness. The range of the free-running period is 17.5 to 31.5 hours.

Mmus\Per2tim.PS shows some rescue of the per01 phenotype; 13.4% of the rescued flies show locomotor activity rhythms in constant darkness. The range of the free-running period is 19.5 to 35 hours.

80-100% of individuals rescued by Mdoa\perper.MM1 show statistically significant rhythms, though the time periods are ~2hr shorter than for per01 rescued by per+t13.2.

Defective circadian locomotor activity periods cannot be rescued by Dpse\perper.P.

Complementation and Rescue Data
Fails to complement
Rescued by
Partially rescued by

per01 is partially rescued by pertim.Aa

per01 is partially rescued by per8.0.pLUC

per01 is partially rescued by perXLG.pLUC

per01 is partially rescued by perCRS.hs

per01 is partially rescued by perCRS.hs.10mut

per01 is partially rescued by perCRS.hs.31mut

per01 is partially rescued by perCRS.hs.69mut

per01 is partially rescued by perΔC2

per01 is partially rescued by perCRS.P\T

per01 is partially rescued by perCRS.hs

per01 is partially rescued by perdel

per01 is partially rescued by per+tCa

per01 is partially rescued by perαTub84B.3'UTR

per01 is partially rescued by perXLG.lacZ

per01 is partially rescued by perClk.t13.2

per01 is partially rescued by per+t13.2

per01 is partially rescued by per+t14.6

Not rescued by

per01 is not rescued by per+t7.2

per01 is not rescued by perhs.PH

per01 is not rescued by per9.0

Comments

per01 adults expressing perS942A.Tag:HA,Tag:polyHis and fed with [15]N exhibit strong behavioral rhythms with periods close to 24 hours in constant darkness (DD) as per01 adults expressing perS942A.Tag:HA,Tag:polyHis and fed with [14]N (controls).

Expression of perTag:HA,Tag:polyHis/+ rescues the arrhythmic locomotor behavior of per01 adults while expression of perTag:HA,Tag:polyHis/perTag:HA,Tag:polyHis, perS951A.T952A.T954A.Tag:HA,Tag:polyHis/+, perS951A.T952A.T954A.Tag:HA,Tag:polyHis/perS951A.T952A.T954A.Tag:HA,Tag:polyHis, perS942A.Tag:HA,Tag:polyHis/+ or perS942A.Tag:HA,Tag:polyHis/perS942A.Tag:HA,Tag:polyHis in per01 background leads to shorter locomotor behavioral rhythms in DD compared to controls.

Expression of perTag:HA,Tag:polyHis rescues the arrhythmic feeding behavior of per01 adults in both LD and DD. Expression of perS942A.Tag:HA,Tag:polyHis in per01 adults leads to a robust feeding behavior with a phase advanced peak in LD while it fails to rescue the arrhythmic feeding behavior of per01 adults in DD.

Transgenic per8:8 flies in a per01 mutant genetic background exhibit sleep patterns very similar to those previously described for wild-type strains, including the temperature and gender differences on daytime sleep.

Expression of perScer\UAS.cYa in neuronal cells (under the control of Scer\GAL4elav-C155) or in circadian cells (under the control of Scer\GAL4tim.PE) rescues daytime temperature preference rhythms in per01 mutant flies.

Expression of perScer\UAS.cYa in M cells, under the control of Scer\GAL4P2.4.Pdf, fails to rescue daytime temperature preference rhythm under light-dark conditions, although a weaker-amplitude rhythm with an abnormal phase is present in these flies.

Expression of perScer\UAS.cYa in both M and E cells with Scer\GAL4cry.PE is unable to rescue daytime temperature preference rhythms under light-dark conditions.

Expression of perScer\UAS.cYa in the DN2 neurons (under the control of Scer\GAL4Clk.int1-3) rescues approximately 46% of the per01 mutant phenotype for daytime temperature preference rhythm.

Expression of perScer\UAS.cYa in the DN2 neurons (under the control of Scer\GAL4Clk.int1-3 and Scer\GAL80Pdf.PS) rescues approximately 66% of the per01 mutant phenotype for daytime temperature preference rhythm.

Expression of perScer\UAS.cYa in DN2 neurons under the control of Scer\GAL4Clk.int1-3 and Scer\GAL80Pdf.PS does not rescue the per01 locomotor activity phenotypes under either light-dark or temperature cycles. These flies are also arrhythmic in dark-dark conditions.

Expression of perScer\UAS.cBa under the control of Scer\GAL4Clk.1.5 partially rescues the circadian locomotor activity defects seen in per01 flies under light-dark conditions; the rescued flies show a robust anticipation of the lights-on transition (morning peak), but evening anticipation is extremely weak and difficult to distinguish from an increase in locomotor activity also observed in control per01 flies at the end of the day.

Expression of perScer\UAS.cBa under the control of Scer\GAL4Clk.1.5 in per01 flies tested under a 12 hours 29[o]C/12 hours 20[o]C thermal cycle in constant darkness rescues the evening activity peak.

per01; per+t7.2 flies display normal experience-dependent increase in sleep. per01; per+t7.2 flies display long-term memory and increase in sleep.

pertG rescues the per01 associated hyperoxia sensitivity and age-related neurodegeneration phenotype.

perT:Ivir\HA1 or perT:Hsap\MYC is able to restore robust and largely temperature compensated behavioral rhythms to per01 flies, both in LD and DD conditions.

In LD conditions, perM560D.T:Ivir\HA1, per01 flies or perM560D.T:Hsap\MYC, per01 flies behave similarly to the controls overall, although behavioural anticipation of the D to L and L to D transitions is less pronounced. In DD conditions, only 30-60% of mutant flies are rhythmic and periods are slightly longer than controls, indicating that the circadian clock is impaired in these flies; however temperature compensation is normal.

perR345E.T:Ivir\HA1, perR345E.T:Hsap\MYC, perW482E.T:Ivir\HA1, perW482E.T:Hsap\MYC, perW482E.M560D.T:Ivir\HA1 or perW482E.M560D.T:Hsap\MYC do not restore rhythmic behaviour to per01 flies in LD or DD conditions in more than 20% of flies. The few rhythmic flies exhibit widely variable periods, and temperature compensation is severely compromised.

Expression of perScer\UAS.cYa under the control of Scer\GAL4elav-C155 can rescue the arrhythmic locomotor activity phenotype of per01 flies, with 65.2% of the rescued flies being rhythmic for locomotor activity.

pertG rescues the per01 associated hyperoxia sensitivity phenotype.

The pronounced circadian rhythm of close-proximity encounters seen in wild-type male:female pairs is lost when the male is hemizygous for per01. This phenotype is not rescued by P{perC7.2}2.

perT:Ivir\HA1,T:Zzzz\His6, per01 flies manifest robust locomotor activity rhythms with periods similar to controls.

perΔ.T:Ivir\HA1,T:Zzzz\His6, per01 flies are arrhythmic.

perT:Ivir\HA1,T:Zzzz\His6 rescues the arrhythmicity seen in per01 flies under constant darkness conditions and the rescued flies have a normal period length (rescues is seen at 18, 25 and 29[o]C). The rescued flies also show normal locomotor activity rhythms under 12 hour light: 12 hour dark conditions.

perSL.T:Ivir\HA1,T:Zzzz\His6 does not the arrhythmicity seen in per01 flies under constant darkness conditions (no rescue is seen at 18, 25 and 29[o]C).

In contrast to wild-type animals, per01 mutants expressing Scer\GAL4P2.4.Pdf driven perScer\UAS.cBa do display locomotor rhythms under constant darkness.

Similarly to wild-type animals, per01 mutants expressing Scer\GAL80Pdf.PS and Scer\GAL4Mai179 or Scer\GAL4cry.PE driven perScer\UAS.cBa do not display locomotor acivity rhythms under constant darkness.

The extension of time spent copulating seen in per01 hemizygous males mated with wild type females is suppressed by per+t13.2 but not by per+t7.2.

perhs.PEa rescues the loss of long term memory in per01 males as assayed by reduction in mating activity in the presence of 5 days after conditioning for 7 hours as long as heat shock is given shortly before conditioning. Time spent in courtship during conditioning is unaffected by pre-conditioning heat shock of these males.

pertim.Aa rescues circadian rhythms in per01 flies to a period that is 1-2 hours shorter than wild type.

The daily locomotor activity profile of per01 flies kept in constant darkness is rescued to wild-type by the presence of a single copy of per+t13.2.

per8.0.T:Ppyr\LUC restores some behavioral rhythmicity to per01 flies kept in 12 hr:12 hr light/dark cycles, especially the characteristic anticipation of the lights-off transition in the evening. However, it fails to rescue any rhythmicity in per01 flies kept in constant darkness following entrainment to 12 hr:12 hr light/dark cycles for 5 days. perXLG.T:Ppyr\LUC restores robust behavioral rhythms in about 50% of per01 flies entrained to 12 hr:12 hr light/dark cycles for 5 days and then released into constant darkness for assay. Under light/dark cycle conditions these flies show synchronized behavioral rhythms similar to those of wild-type controls.

The locomotor arrhythmicity phenotype is not rescued by perninaE.T:Ivir\HA1.

The abnormal locomotor activity behaviour of per01 flies is not rescued by perSG.T:Ecol\lacZ or perBG.T:Ecol\lacZ, and is partially rescued by perXLG.T:Ecol\lacZ.

per+t7.2 can rescue circadian behavioural rhythms of per01 flies.

The arrhythmicity of per01 flie can be rescued by perClk.t13.2. per01 flies carrying perClk.t13.2 have a shorter period of locomotor activity than wild-type flies.

Rhythmic deficits can be rescued by P-element mediated introduction of per+t13.2, perS589G, perS589T, perS589D, perS589Y, perS589E, perM.T:Hsap\MYC, perC.T:Hsap\MYC, perC.T:Ivir\HA1 and perN.T:Ivir\HA1 constructs.

The locomotor activity rhythm phenotype is not rescued by perSG.T:Ecol\lacZ.

Images (0)
Mutant
Wild-type
Stocks (6)
Notes on Origin
Discoverer

Konopka, Benzer.

Comments
Comments

Adenylate cyclase activity normal.

per01 and perClk map approximately 0.015 map units apart from each other.

Expression of P{rh-per} did not alter the arrhythmic cycles.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (13)
Reported As
Symbol Synonym
per01
(Barber et al., 2021, Dapergola et al., 2021, Kula-Eversole et al., 2021, Song et al., 2021, Zhang et al., 2021, Alpert et al., 2020, Öztürk-Çolak et al., 2020, Ulgherait et al., 2020, Wiggin et al., 2020, Delventhal et al., 2019, Liang et al., 2019, Martin Anduaga et al., 2019, Schlichting et al., 2019, Stone et al., 2019, Beck et al., 2018, Chen et al., 2018, Fujiwara et al., 2018, Shakhmantsir et al., 2018, Yadlapalli et al., 2018, Beckwith et al., 2017, De Nobrega et al., 2017, Kijak and Pyza, 2017, Kim et al., 2017, King et al., 2017, Li et al., 2017, Zhao and Karpac, 2017, De Nobrega and Lyons, 2016, Landgraf et al., 2016, Cao and Edery, 2015, Chen et al., 2015, Flourakis et al., 2015, Gill et al., 2015, Head et al., 2015, Thimgan et al., 2015, Yildirim et al., 2015, Chen et al., 2014, Guo et al., 2014, Hermann-Luibl et al., 2014, Liu et al., 2014, Long et al., 2014, Seki and Tanimura, 2014, Vrailas-Mortimer et al., 2014, Garbe et al., 2013, Li and Rosbash, 2013, Szabó et al., 2013, Beaver et al., 2012, Chen et al., 2012, Kaneko et al., 2012, Krishnan et al., 2012, Low et al., 2012, Lim et al., 2011, Yu et al., 2011, Ko et al., 2010, Kula-Eversole et al., 2010, Ruiz et al., 2010, Sun et al., 2010, Donlea et al., 2009, Johard et al., 2009, Kotwica et al., 2009, Krishnan et al., 2009, Landskron et al., 2009, Yu et al., 2009, Benito et al., 2008, Fernandez et al., 2008, Fujii et al., 2008, Kadener et al., 2008, Krishnan et al., 2008, Low et al., 2008, Tanoue et al., 2008, Codd et al., 2007, Fang et al., 2007, Kadener et al., 2007, Kim et al., 2007, Ko et al., 2007, Matsumoto et al., 2007, Mehnert et al., 2007, Collins et al., 2006, Houl et al., 2006, Yu et al., 2006, Yoshii et al., 2005, Majercak et al., 2004, Shigeyoshi et al., 2002, Stanewsky et al., 2002, Blanchardon et al., 2001, Darlington et al., 2000, Lyons et al., 2000)
per0
(Cusumano et al., 2019, Lee et al., 2019, Li et al., 2019, Xue et al., 2019, Fropf et al., 2018, Górska-Andrzejak et al., 2018, Yang and Edery, 2018, Selcho et al., 2017, Cavey et al., 2016, Chen and Rosbash, 2016, Petsakou et al., 2015, Fan et al., 2013, Huang et al., 2013, Grima et al., 2012, Ling et al., 2012, Ruben et al., 2012, Tanenhaus et al., 2012, Chiu et al., 2011, Diangelo et al., 2011, Blanchard et al., 2010, Zhang et al., 2010, Górska-Andrzejak et al., 2009, Johard et al., 2009, Picot et al., 2009, Rieger et al., 2009, Chiu et al., 2008, Richier et al., 2008, Yoshii et al., 2008, Picot et al., 2007, Van Gelder, 2006, Wijnen et al., 2006, Lin et al., 2005, Mazzoni et al., 2005, Schoning and Staiger, 2005, Busza et al., 2004, Grima et al., 2004, Levine, 2004, Kim et al., 2002, Levine et al., 2002, Panda et al., 2002, Bao et al., 2001, Claridge-Chang et al., 2001, Helfrich-Forster, 2001, Hendricks et al., 2001, Jackson et al., 2001, Martinek et al., 2001, Rosato and Kyriacou, 2001, Su et al., 2001, Williams et al., 2001, Andretic and Hirsh, 2000, Hendricks et al., 2000, Lakin-Thomas, 2000, Schotland et al., 2000, Andretic et al., 1999, Belvin et al., 1999, Blumenthal and Block, 1999, Curtis et al., 1999, Giebultowicz, 1999, Ishikawa et al., 1999, Tyson et al., 1999, Alt et al., 1998, Emery et al., 1998, Price et al., 1998, Rutila et al., 1998, Tomioka et al., 1998, Wilsbacher and Takahashi, 1998, Giebultowicz and Hege, 1997, Greenspan, 1997, Rouyer et al., 1997, Sakamoto et al., 1997, Suri et al., 1997, Dunlap, 1996, Myers et al., 1996, Sehgal et al., 1996, van Gelder and Krasnow, 1996, van Gelder and Krasnow, 1996, Dowse et al., 1995, Levine et al., 1995, Myers et al., 1995, Price, 1995, Price et al., 1995, Sehgal, 1995, van Gelder et al., 1995, Hirsch and Tompkins, 1994, Helfrich-Forster and Homberg, 1993, Price et al., 1993, Takahashi, 1993, Takahashi, 1992, Baylies and Young, 1991, Dowse et al., 1990, Livingstone et al., 1984, Smith and Konopka, 1981, Konopka, 1979)
Name Synonyms
Secondary FlyBase IDs
    References (339)