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General Information
Symbol
Dmel\TbhnM18
Species
D. melanogaster
Name
FlyBase ID
FBal0061578
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
TΒHnM18, TβHM18, TbhM18
Key Links
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

Small deletion in the ATG region of Tbh.

Imprecise excision of the P{lacW} insertion deleting flanking genomic sequences.

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

TbhnM18 homozygous adults exhibit a significant decrease in sleep during night time (with significantly decreased bout duration but not number) while they do not exhibit any changes in sleep during day time (duration, bout number or bout duration) when compared to controls. Also sleep recovery rate after mechanical deprivation is significantly increased compared to controls.

TbhnM18 homozygous mutant adult females (mated or virgin) display defects in trimming of posterior follicle cells and produce fewer trimmed eggs.

TbhnM18 flies have a significant short term olfactory memory defect following training with sucrose, compared to controls; memory at later time-points is statistically indistinguishable from controls.

TbhnM18/TbhnM18 larvae show a significant decrease in stimulus evoked transmitter release and a significant increase in the amplitude of spontaneous mEJPs (no significant difference in paired pulse plasticity) at the neuromuscular junction, compared to controls.

The majority of Gr32a-expressing neurons reach the suboesophageal ganglion in TbhnM18 mutant males, but some aberrant termination of Gr32a-expressing axons in the antennal lobe region is seen.

Mutant males show reduced aggressive behavior (significantly increased latency to the first lunge and significantly reduced number of lunges) compared to controls. The mutant males show significantly increased levels of male-male courtship compared to controls.

TbhnM18 mutant flies, which lack octopamine, display water learning that is indistinguishable from that of control flies.

Virgin TbhnM18 mutant females show increased receptivity compared to wild type virgin females. Mated TbhnM18 mutant females lay very few eggs and remain highly receptive after copulation, displaying low levels of rejection behaviors such as ovipositor extrusion compared with mated controls. Wild type males court TbhnM18 mated females significantly more than wild type mated females. Heterozygous TbhnM18/+ females also show increased receptivity compared to controls, but to a lesser extent than homozygotes. Egg laying in heterozygotes remains normal. Feeding octopamine to 1 day old virgin homozygous TbhnM18 mutant flies triggers post-mating responses and induces egg laying in the absence of copulation.

In contrast to wild type, mutant flies do not show a preference for ethanol-containing food odors (over food odors without ethanol) in an olfactory choice assay. Mutant flies prefer food odors over water, and ethanol over water. They show a reduced preference for ethanol vs water compared to wild-type controls.

TbhnM18 homozygous female and hemizygous male larvae have a significant reduction in the distance they crawl, relative to controls.

Mutant males show significantly impaired courtship conditioning compared to wild-type males.

TbhnM18 mutant third instar larvae exhibit type II neuromuscular junction endings with an increase in the number of synaptopods (dynamic filopodia-like extensions).

TbhnM18 mutant third instar larval neuromuscular junctions exhibit a decrease in the number of type II boutons and terminal branches.

TbhnM18 third instar larvae exhibit a significant decrease in EJP amplitude.

TbhnM18 third instar larvae exhibit a <5% increase in locomotor speed in response to starvation for 2 hours, compared to a 36% increase in wild-type.

The elimination of octopamine in TbhnM18 mutants results in a significant decrease in natural synaptopods. Addition of octopamine in TbhnM18 mutants fails to induce an increase in synaptopods.

TbhnM18 mutants exhibit a decrease in the number of type II boutons. The absence of type II innervation leads to a substantial reduction in the number of type I boutons.

TbhnM18 flies exhibit strongly reduced appetitive olfactory memory performance levels in sugar-reward assays. However, TbhnM18 mutant flies exhibit wild-type levels of memory performance in heat-box chamber assays.

TbhnM18 flies do not exhibit a difference in locomotor activity compared to wild-type in heat-box walking assays.

TbhnM18 flies do not exhibit any changes in the wild-type pre-exposure effect on associative place memory.

Mutant flies show an impairment in reward learning after odour-sugar training using the odours 3-octanol and 4-methylcyclohexanol, although residual reward learning ability is still detectable.

Mutant flies show a complete loss of reward learning ability after odour-sugar training using the odours n-amyl acetate and isoamyl acetate.

Mutant flies show fully intact reward learning after odour-sugar training using the odours 3-octanol and benzaldehyde.

In a modified punishment learning procedure, which is identical to the reward learning procedure except that sugar presentation is replaced by pulses of electric shock, the mutant flies behave comparably to controls, both when the odours 3-octanol and 4-methylcyclohexanol and n-amyl acetate and isoamyl acetate are used.

Mutant flies show normal relief learning ability when the odours 3-octanol and 4-methylcyclohexanol are used.

Fighting latency is prolonged in mutant males when two males are placed in a small closed chamber containing a food pad in the centre. The frequency of lunging and holding is reduced in the mutant males in this assay compared to controls. When a wild-type male is paired with a mutant male in the aggression assay, the wild-type males still fight with the mutant males, whereas the mutants do not initiate fighting and do not fight back.

Fighting latency is prolonged in mutant females when two females are placed in a small closed chamber containing a food pad in the centre. Head butting frequency is reduced in the mutant females in this assay compared to controls.

When a mutant male and a wild-type male are placed in a chamber with a wild-type virgin female in a mating competition assay, the wild-type males mate more than the mutant male. In addition, the mutant males spend significantly less time than the wild-type males on the central food pad in this assay.

Mutant males show normal locomotor activity. Mutant males show normal avoidance of benzaldehyde in an odour-sensitivity assay.

Mutant males behave similarly to wild-type males in showing sexual preference toward decapitated females over decapitated males.

Mutant and wild-type males have similar courtship indices, initiation latencies and mating latencies in a typical male-female courtship assay. The frequency of unilateral wing vibration (an early step in courtship) is indistinguishable between mutant and wild-type males, whereas mutant males show a significant reduction in the frequency of wing threat (bilateral wing extension, a typical step in aggression). Mutant males do not show significant male-male courtship.

TbhnM18 flies exhibit an approximately eightfold increase in tyramine concentration and completely lack Octapamine. TbhnM18 females are sterile, due to their inability to lay eggs. Otherwise the flies appear normal, without dramatic effects on their behavior or lifespan.

TbhnM18 mutants show a drastic decrease in the initial flight duration, in all subsequent flight episodes, and thus also in total flight duration. Mutants resume flight less often after stimulation compared with control animals. TbhnM18 mutants take off significantly less often in response to wind stimulation than wild-type controls and, once airborne, they fly for significantly shorter durations. Wing-beat amplitudes and wing-beat frequencies are similar in TbhnM18 mutants and wild-type controls. On the muscular level, sarcomere length of the dorsal longitudinal flight muscle is not affected in TbhnM18 mutants. Feeding mutant flies with octopamine rescues the flight behavior phenotype. Sarcomere lengths are similar in wild-type TbhnM18 and TbhnM18 mutants rescued by feeding octapamine.

Feeding TbhnM18 mutant flies with the α2-adrenergic receptor antagonist YH rescues flight initiation and maintenance.

Adult male TbhnM18 flies show normal locomotor activity compared to controls. This is in contrast to TbhnM18 larvae, which show locomotor deficits compared with controls.

TbhnM18 adults show wild-type behavioral responses to cocaine.

TbhnM18 mutant larvae travel less distance than control larvae.

TbhnM18 mutants are in forward locomotion only ~35% of the time, compared to ~80% for wild-type larvae.

Regular rhythmic activity is less common in TbhnM18 mutants compared to control larvae. Only 25% of TbhnM18 larvae show spontaneous bursting activity (compared to 88% in the revertant TbhrM6 and 85% in wild-type). Instead, there is a high level of tonic nerve activity with very few bursts. These bursts have a similar spindle shape as controls, with larger amplitude neurons firing near the end of the bursts.

Rhythmic nerve bursting activity and muscle contraction waves are rare in TbhnM18 mutants.

Nerve spiking bursts, associated with waves of body-wall contractions, are rare in TbhnM18 mutants compared to wild-type. These locomotive contraction waves are often isolated, not part of a regular rhythmic pattern, as in wild-type. Only occasional intersegmentally co-ordinated bursts are seen, generating an anterior to posterior (or vice versa) contraction wave, consistent with the lack of linear locomotion pattern in TbhnM18 mutant larvae. Most bursts are associated with isolated local, nonpropagated contractions. For bursts associated with propagating waves, there are no obvious differences from wild-type in the co-ordination of activities bilaterally within a single segment or unilaterally from nerves innervating anterior and posterior segments.

Non-rhythmic activity that is not associated with regular waves of body-wall contractions is more frequent in TbhnM18 mutants that have reduced OA and increased TA levels, compared to wild-type. On average, TbhnM18 mutants have 80% fewer bursts per minute than the wild-type larvae and 65% fewer bursts than the TbhnM18 revertants. In addition, bursts in TbhnM18 mutants are less likely to be part of a regular rhythmic pattern.

TbhnM18 mutants express non-rhythmic bursting activities significantly more often than control larvae. TbhnM18 mutants spend approximately 93.6% of the time in non-rhythmic activities, whereas TbhrM6 revertant and wild-type larvae exhibit non-rhythmic activities approximately 46.6% and 34.4% of the time, respectively. TbhnM18 mutants produce regular rhythmic patterns 7% of the time, with these locomotor contraction waves divided equally between posterior-to-anterior and anterior-to-posterior. In contrast, wild-type or revertant larvae are much more likely to generate posterior-to-anterior locomotive waves.

It is very rare for rhythmic bursting activity to persist for >5 or >10 bursts in TbhnM18 mutants, despite this being a common occurence in wild-type.

Segmental nerves of TbhnM18 mutants appear to be bilaterally co-ordinated, but bursts of activity associated with co-ordinated waves of contractions are rare in these mutants.

EJCs recorded from the ventral muscle 6/7, lateral muscle 4, or dorsal muscle 2 are organised into a bursting-like pattern for both wild-type larvae and TbhnM18 mutants. In general, the activity pattern of clustered EJCs is similar for simultaneous recordings from muscle pairs (e.g. ventral muscle 6/7 with lateral muscle 5, and muscle 6/7 with dorsal muscle 2). However, the temporal co-ordination of the muscle pairs appears to be tighter in wild-type larvae than TbhnM18 mutants.

The average number of strides produced by crawling larvae is 10 times lower in TbhnM18 mutants compared to wild-type controls.

Tapping the ventral midline with a silver wire near the head of TbhnM18 mutant larvae produces a dramatic effect. The ongoing nerve activity for all TbhnM18 mutants consists primarily of nonrhythmic spiking activities that are not associated with contraction waves. Touching the head of TbhnM18 mutants with a silver wire produces an extended burst in segmental nerve 3 that is associated with a contraction of the anterior body regions and not a locomotive contraction wave. Most strikingly, the contraction is followed by alternating bursts, in nerves 3 and 7, that are associated with anterior to posterior waves. Touching the tail of TbhnM18 mutant larvae initiates extended contractions and bursts in posterior segments of TbhnM18 larvae. This is followed by a rhythmic nerve activity pattern corresponding to contraction waves that proceed from posterior to anterior body segments. This demonstrates that the CNS of TbhnM18 mutants is capable of generating the motor program necessary for locomotion within a short period after sensory stimulation.

Control flies which are preexposed to a heat shock show a 46 +/- 4% increase in mean elution time (MET) when exposed to ethanol in an inebriometer 4 hours later. This heat-ethanol cross tolerance is also seen in TbhnM18 flies. Mutant flies do not show any changes in lifespan, as compared to controls. However, these flies have a reduced ability to develop tolerance to ethanol vapour as compared to controls (22 +/- 5% increase in MET after pre-exposure to ethanol compared to an increase of 34 +/- 7% for control flies) when assayed using an inebriometer.

Mutant 1 day old males and females do not differ from wild type in their survival following 4 hours heat stress (38oC). Mutant 6 day old females do not differ from wild type in their survival following 4 hours heat stress (38oC).

Homozygous mated females do not deposit eggs and have swollen abdomens with ovaries full of late stage oocytes that remain even in 20 day old flies. The ovarioles of mature mated females contain 4 to 5 stage 14 oocytes (instead of the normal 1 or 2) and oocytes between stages 7 and 13 are essentially missing (this phenotype is a characteristic of "backed-up" ovarioles that are generated when egg laying is inhibited). Eggs are never seen in the lower genital tract (uterus or ovipositor) of the mutant females. The females extrude their ovipositor and contract their abdomen, but never extrude an egg even if the abdomen in mechanically squeezed. These phenotypes indicate that the defect is in ovulation rather than in oviposition. Virgin homozygous females also do not deposit eggs (in contrast to wild-type virgin females).

TbhnM18 mutants learn to avoid odors that they have previously experienced with an electric shock to the same extent as wild type flies but they are unable to learn to be attracted to odors that they have previously experienced with a sugar reward. When TbhnM18 flies have been fed with octopamine for 1 hour, they can learn to be attracted to sugar-associated odors at the same rate as wild-type controls. If octopamine is fed to the flies after the odor-training period, it has no effect on their sugar memory. TbhnM18 flies have the same sensory response to sugar as wild-type flies.

TbhnM18 males are virtually non-aggressive in a behavioural assay.

Under normal conditions, 1 or 6 day old mutant females show a significantly higher juvenile hormone (JH)-hydrolysing activity compared to wild-type females. Mutant and wild-type females exposed to 38oC show a significant decrease in JH-hydrolysing activity compared to control females at 25oC. 1 day old mutant females have lower levels of stress reactivity (calculated as the percent decrease in JH-hydrolysing activity at 38oC relative to normal conditions) than control females. 6 day old mutant females have significantly higher levels of stress reactivity than control females.

Mutants exhibit a reduced tolerance to ethanol.

TbhnM18 mutant flies show wild-type sensitization to cocaine.

Mutants survive to adulthood and exhibit normal external morphology. Females mate but retain the fully developed normal oocytes. The egg retention defect is associated with the octopamine deficit, mated gravid females initiate egg laying when transferred onto octopamine supplemented food.

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

TbhnM18 is a non-enhancer of abnormal memory | adult stage | heat sensitive phenotype of Scer\GAL4GMR58E02, TrpA1UAS.(B).cKa

Suppressor of
Statement
Reference

Tbh[+]/TbhnM18 is a suppressor of chemical resistant | dominant phenotype of BaccKG08597

NOT Suppressor of
Statement
Reference

TbhnM18 is a non-suppressor of abnormal memory | adult stage | heat sensitive phenotype of Scer\GAL4GMR58E02, TrpA1UAS.(B).cKa

Other
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference

TbhnM18/+ completely restores normal ethanol sensitivity in BaccKG08597/+ animals.

Expression of TrpA1Scer\UAS.(B).cKa under the control of Scer\GAL4Tdc2.PC in a TbhnM18 background at 31[o]C contingent with odour presentation does not induce the formation of appetitive olfactory memory.

Expression of TrpA1Scer\UAS.(B).cKa under the control of Scer\GAL40104 at 31[o]C contingent with odour presentation is sufficient to form appetitive olfactory memory even in a TbhnM18 background.

The body size of males expressing frudsRNA.M.Scer\UAS driven by Scer\GAL4Tdc2.PC in a TbhnM18 mutant genetic background is smaller than that of wild-type or Scer\GAL4Tdc2.PC/frudsRNA.M.Scer\UAS males.

TbhnM18 mutant males expressing frudsRNA.M.Scer\UAS under the control of Scer\GAL4Tdc2.PC courted second males more frequently than TbhnM18 single mutants or flies expressing frudsRNA.M.Scer\UAS alone. Male-to-male wing extension duration is significantly increased in TbhnM18 mutant males expressing frudsRNA.M.Scer\UAS under the control of Scer\GAL4Tdc2.PC compared with progenitor lines (i.e. flies either expressing frudsRNA.M.Scer\UAS under the control of Scer\GAL4Tdc2.PC in a wild-type background or mutant for TbhnM18).

Ethanol tolerance is almost completely abolished in hangAE10 TbhnM18 double mutant flies.

Xenogenetic Interactions
Statement
Reference

A TbhnM18 background eliminates the increase in locomotor speed seen upon blue light stimulation of octopaminergic neurons expressing Crei\ChR2Scer\UAS.cSa, under the control of Scer\GAL4Tdc2.PC.

Complementation and Rescue Data
Partially rescued by
Comments

Expression of TbhScer\UAS.cSa under the control of either Scer\GAL4Tdc2.PC, Scer\GAL4NP7088 or Scer\GAL4Feb15 rescues the loss of olfactory ethanol preference seen in TbhnM18 flies.

Expression of TbhScer\UAS.cSa under the control of Scer\GAL4Tdc2.PC in the presence of Scer\GAL80Cha.PK does not rescue the loss of olfactory ethanol preference seen in TbhnM18 flies.

Expression of TbhScer\UAS.cSa under the control of Scer\GAL4Tbh.6.2 partially rescues the loss of olfactory ethanol preference seen in TbhnM18 flies.

The courtship conditioning defects seen in TbhnM18 males are rescued by expression of TbhScer\UAS.cMa under the control of Scer\GAL4Tdc2.PC.

Expression of TbhScer\UAS.cMa under the control of Scer\GAL4C57 rescues the increase locomotion elicited by food deprivation and the concurrent increase in neuromuscular junction synaptopods.

Expression of TbhScer\UAS.cMa in octopaminergic neurons under the control of Scer\GAL4Tdc2.PC rescues the drop in type I and type II boutons and terminal branches seen in TbhnM18 mutant third instar larval neuromuscular junctions.

Expression of TbhScer\UAS.cMa under the control of Scer\GAL4Tdc2.PC reduces the aggression deficiency that is seen in TbhnM18 males; fighting latency is shortened and the frequencies of both lunging and high-intensity fighting (holding, boxing and tussling) are increased in the rescued flies in an aggression assay. Expression of TbhScer\UAS.cMa under the control of Scer\GAL4Tdc2.PC also effectively rescues the aggression phenotype of TbhnM18 females.

Expression of TbhScer\UAS.cMa under the control of either Scer\GAL4Tdc1.PC, Scer\GAL4c309, Scer\GAL4MJ286 or Scer\GAL4Cha.7.4 fails to rescue the reduced aggression phenotypes of TbhnM18 males.

Expression of TbhScer\UAS.cMa under the control of Scer\GAL4Tdc2.PC in the presence of the Scer\GAL80Cha.PK repressor (which inhibits Scer\GAL4 in the Cha expression domain) rescues the reduced aggression phenotypes of TbhnM18 males.

Expression of Tbhhs.PS through heat-shock rescues flight initiation and maintenance in TbhnM18 mutants. No rescue is seen without heat-shock.

Following heat shock, the Tbhhs.PS transgene rescues the sugar memory phenotype of TbhnM18 flies.

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Stocks (0)
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External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (19)
References (55)