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General Information
Symbol
Dmel\Itprug3
Species
D. melanogaster
Name
FlyBase ID
FBal0156341
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
ug3
Key Links
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Nucleotide change:

C5528719T

Reported nucleotide change:

C?T

Amino acid change:

S223F | Itp-r83A-PA; S223F | Itp-r83A-PB; S223F | Itp-r83A-PC

Reported amino acid change:

S224F

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

Amino acid replacement: S224F. Nucleotide substitution: C?T.

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

Itprug3/Itprwc703 and Itprug3/Itprwc361 adults show a "spread out" wing posture.

Itp-r83Aug3 heterozygosity does not affect the baseline mEPSP amplitude or distribution in larval NMJ neurotransmission, as compared to controls.

Itp-r83Aug3/+ flies have normal wing structure.

itgr[ku] flies (Itp-r83Aka1091/Itp-r83Aug3) are resistant to starvation, but show a wild type response to oxidative stress. Females survive longer than males. As in wild type, this resistance to starvation is reduced when flies are fed media containing the lipase inhibitor Orlistat. In contrast to controls, there is no visible change in lipid levels up to 72 hours after starvation in the abdominal fat body cells. A significant increase in the number and volume of lipid droplets is also seen in fed flies, and this is reduced on starvation. itgr[ku] flies also have increased body weight and climbing ability is slightly reduced compared to controls.

At 0 hours post-eclosion, itgr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutants and wild type have similar levels of abdominal triacylglycerols (TAGs). However, three days after feeding on a normal diet, the levels of TAGs in itpr[ku] are nearly double those of wild type. When adult flies are starved for 72 hours TAG levels drop significantly in wild type, but in itpr[ku] the drop is minimal. As in controls, the level of abdominal TAGs is reduced when flies are fed media containing the lipase inhibitor Orlistat, but the levels do not reduce to wild type levels. Orlistat also reduced TAG deposits in the midgut.

The overall size of itpr[ku] (Itp-r83Aka1091/Itp-r83Aug3) females is similar to controls, but a small but significant reduction in wing size is observed. The number of sensory hairs along the wing margin is not significantly different from controls.

The increase in the proportion of long chain fatty acids (LCFAs) seen in starved control flies compared to their well-fed equivalents is not seen in itpr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant flies. The proportion of LCFAs remained the same or showed a tendency to decrease in itpr[ku] starved adults compared to well fed flies.

itpr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant females ingest three times as much food as wild type. This hyperphagia is accompanied by deposition of excess neutral lipids in the mid-gut epithelium.

itgr[wu] flies (Itp-r83Awc703/Itp-r83Aug3) are resistant to starvation, but show a wild type response to oxidative stress. Females survive longer than males.

The ratio of TAGs to total protein in itpr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant pupae is higher than in wild type. Selected membrane lipid classes are reduced when compared to total TAG levels; phosphatidylethanolamines (PE), phosphatidylcholines (PC), phosphatidylinositols (PI), phosphatidylserines (PS), ceramides (Cer) and ceramide phosphorylethanolamines (CerPE). The ratio of membrane lipids to total protein content is unchanged.

Itp-r83Aug3 does not extend the lifespan of wild-type flies.

Itp-r83Aka1091/Itp-r83Aug3 and Itp-r83Awc703/Itp-r83Aug3 animals have wing posture, flight and flight physiology defects.

Itp-r83Asv35/Itp-r83Aug3 third instar larvae are significantly reduced in body size and fat body content.

The majority of Itp-r83Asv35/Itp-r83Aug3 mutant larvae ingest no or very little food compared to wild-type larvae, and defects in feeding behaviour are more prevalent in animals 108 hours after egg laying compared to 60 hours after egg laying.

There is no significant difference in the total number of salivary gland cells from Itp-r83Asv35/Itp-r83Aug3 larvae compared to wild-type larvae at 60 hours after egg laying.

Expression of Itp-r83AScer\UAS.cVa under the control of Scer\GAL4Ilp2.PR in Itp-r83Asv35/Itp-r83Aug3 flies results in significantly larger pupal size compared to wild-type pupae, and adult flies are also increased in size. There is a significant increase in the time taken to pupate by mutant larvae compared to wild-type.

Expression of Itp-r83AScer\UAS.cVa under the control of Scer\GAL4Ddc.PL in Itp-r83Asv35/Itp-r83Aug3 flies results in increased pupal length, body size, and adult fly weights. There is a significant increase in the time taken to pupate by mutant larvae compared to wild-type.

Itp-r83Asv35/Itp-r83Aug3 animals expressing Itp-r83AScer\UAS.cVa under the control of Scer\GAL412.1 and either Scer\GAL4Ilp2.PR or Scer\GAL4Ddc.PL have more surviving pupae, and pupate 12-20 hours earlier than when expression is driven by Scer\GAL4Ilp2.PR or Scer\GAL4Ddc.PL alone. Pupal and adult fly sizes in mutant animals expressing Itp-r83Asv35/Itp-r83Aug3 animals expressing Itp-r83AScer\UAS.cVa under the control of Scer\GAL412.1 and either Scer\GAL4Ilp2.PR or Scer\GAL4Ddc.PL are comparable to that of wild-type animals.

Itp-r83Aka1091/Itp-r83Aug3 mutants exhibit an altered wing posture.

Itp-r83Aka1091/Itp-r83Aug3 mutants are cold-sensitive and lethal during the third-instar larval stage at 17.5[o]C. SOCE and '[Ca[2+]'][[ER]] in these conditions are similar to wild-type neurons grown under identical conditions at 17.5[o]C.

Primary neurons from Itp-r83Aka1091/Itp-r83Aug3 mutant larval brains exhibit a greatly diminished SOC influx, whereas '[Ca[2+]'][[ER]] is significantly elevated in neurons derived from Itp-r83Aka1091/Itp-r83Aug3 larvae grown at 25[o]c, compared to wild-type. The mean '[Ca[2+]'][[ER]] in Itp-r83Aka1091/Itp-r83Aug3 mutants appears twice as eleavated as n wild-type. The percentage of cells with detectable soc is ~3-5%, as compared with 70-80% in wild-type.

Microsomes prepared from either adult or larval heads of Itp-r83Aka1091/Itp-r83Aug3 animals show lower levels of Ca[2+] release after after InsP3 stimulation compared to microsomal vesicles from wild-type animals of a comparable developmental stage.

Itp-r83Aka1091/Itp-r83Aug3 is lethal at 17'C but not at 25'C. The resulting adults have an abnormal wing posture.

Itp-r83Awc703/Itp-r83Aug3 and Itp-r83Aka1091/Itp-r83Aug3 flies show a "down-turned" wing phenotype. Itp-r83Asa54/Itp-r83Aug3 transheterozygotes exhibit a partially penetrant phenotype of crumpled wing margins.

Indirect flight muscles of wild-type flies can express short bursts of electrical activity that are associated with cleaning behavior. Itp-r83Awc703/Itp-r83Aug3 and Itp-r83Aka1091/Itp-r83Aug3 flies show an increase in spontaneous firing from these muscles, which is unrelated to cleaning behavior. The indirect flight muscles of these mutants fail to produce firing patterns in response to an air puff, which occurs in wild-type muscles. The giant fiber pathway appears to have the same properties in Itp-r83Aka1091/Itp-r83Aug3 mutants as in wild type.

The majority of Itp-r83Aug3/Itp-r83Aka901 larvae die in the second instar, by 176-184 hours after egg laying. When Itp-r83Aug3/Itp-r83Aka1091 animals are grown at 15oC, development appears normal with low levels of pupal lethality. At 17.5oC almost all larvae die during the second instar, those few that do molt into third instar do so later than controls. Occasionally a few late pupae are also seen. Larvae exhibit lethality when shifted from 25oC to 17.5oC as second instars at 48-56 hr after egg laying (AEL), but not when shifted as third instars at 80-88 hrs AEL. Shifting the larvae back into 25oC as late second instars at 164-172 AEL does not improve viability.

Itp-r83Awc361/Itp-r83Aug3 transheterozygotes are adaptation response defective. The response of homozygous Itp-r83Aug3 animals to all concentrations of ethyl acetate is normal.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement
Reference

Itprug3/Itprka1091 has lethal | cold sensitive phenotype, suppressible by Ca-P60A[+]/SERCAKum170

Itprug3/Itprka1091 has flightless | partially phenotype, suppressible | partially by Ca-P60A[+]/SERCAKum170

NOT suppressed by
Statement
Reference

Itprwc361/Itprug3, Orai[+]/Oraik11505, SERCA[+]/SERCAKum170 has abnormal flight phenotype, non-suppressible by NUCB1c01508/NUCB1[+]

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

Itprug3/Itp-r83A[+] is a suppressor of wing phenotype of IP3K2wy-1

Itprug3/Itp-r83A[+] is a suppressor | partially of wing phenotype of IP3K2wy-2

Itprug3/Itp-r83A[+] is a suppressor | partially of wing phenotype of IP3K2wy-74i

Additional Comments
Genetic Interactions
Statement
Reference

Female larvae expressing cacRQ,SL.UAS.EGFP under the control of Scer\GAL4elav-C155 exhibit a significant increase in NMJ mEPSP amplitude and frequency; the increased amplitude is partially suppressed by Itp-r83Aug3 heterozygosity; the gigantic spontaneous events are also diminished.

Itp-r83Aug3/+ suppresses wing phenotypes seen in IP3K2wy-1/IP3K2wy-1 flies, and partially suppresses wing phenotypes in IP3K2wy-2/IP3K2wy-2 or IP3K2wy-74i/IP3K2wy-74i flies.

Expression of Ilp2Scer\UAS.cBa in the insulin-producing cells under the control of Scer\GAL4Ilp2.PR rescues the starvation resistance and mobilization of TAGs from abdominal fat body cells seen in itgr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant flies to wild type levels. The increase in body weight and stored TAG levels are only partially rescued.

Expression of Ilp2Scer\UAS.cBa in the insulin-producing cells under the control of Scer\GAL4Ilp2.PR partially restores the profile of TAGs and their constituent fatty acids in Itp-r83Aka1091/Itp-r83Aug3 mutants to that of the wild type under starvation.

Expression of Ilp2Scer\UAS.cBa in the insulin-producing cells under the control of Scer\GAL4Ilp2.PR partially suppresses the overeating seen in itgr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant females.

Expression of Pi3K92EScer\UAS.T:Hsap\MYC,T:Hsap\CAAX in the fat body under the control of Scer\GAL4c729 partially rescues the starvation resistance phenotype seen in itgr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant flies. Expression of Pi3K92EScer\UAS.T:Hsap\MYC,T:Hsap\CAAX leads to reduced levels of stored TAGs and their mobilization upon starvation as compared to itgr[ku] alone. The increase in body weight is only partially rescued.

Expression of bskK53R.Scer\UAS in the insulin-producing cells under the control of Scer\GAL4Ilp2.PR rescues the starvation resistance seen in itgr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant flies.

Itp-r83Aug3 partially suppresses the climbing defect of 15-day old Scer\GAL4Toll-6-D42>Hsap\TARDBPScer\UAS.cHa flies and extends their median lifespan by 6.5days.

Co-expression of StimScer\UAS.cAa and olf186-FScer\UAS.cZa driven by Scer\GAL4Ilp2.PR completely suppresses the wing posture, flight and flight physiology defects of Itp-r83Aka1091/Itp-r83Aug3 flies.

Expression of olf186-FScer\UAS.cZa in Ilp2 neurons (under the control of Scer\GAL4Ilp2.PR) partially suppresses the altered wing posture of Itp-r83Aka1091/Itp-r83Aug3 mutants. Although flight ability is not restored, flight patterns are initiated on air-puff delivery, while these are normally completely lacking in Itp-r83Aka1091/Itp-r83Aug3 mutants. Spontaneous hyperactivity of the DLMs in Itp-r83Aka1091/Itp-r83Aug3 mutants is suppressed to a significant extent by expression of olf186-FScer\UAS.cZa either ubiquitously (Scer\GAL4hs.PB at 25[o]C) or in the aminergic (Scer\GAL4Ilp2.PR) and glutamatergic subneuronal domains (Scer\GAL4OK371).

Ubiquitous expression of olf186-FScer\UAS.cZa under the control of Scer\GAL4hs.PB in Itp-r83Aka1091/Itp-r83Aug3 mutants, up-regulated by a heat shock either in 24hr pupae or in 1-day-old adults results in a significant number of flies initiating flight in response to an air puff. Thus, levels of olf186-FScer\UAS.cZa can modulate flight circuit activity both during its development and in adult function. However, the flight patterns obtained are not sustained and appear arrhythmic, indicating that although olf186-FScer\UAS.cZa overexpression can suppress the flight defects and associated physiology of Itp-r83Aka1091/Itp-r83Aug3 mutants to a significant extent, it is insufficient to regain complete flight.

Pan-neural overexpression of olf186-FScer\UAS.cZa in Itp-r83Aka1091/Itp-r83Aug3 neurons restores detectable SOCE to 70%, as in wild-type. Also, '[Ca[2+]'][[ER]] is restored to wild-type levels, indicating that reduced SOCE and elevated '[Ca[2+]'][[ER]] in Itp-r83Aka1091/Itp-r83Aug3 are linked homeostatic processes.

Introduction of a single copy of olf186-Fk11505 suppresses the cold-sensitive lethality found in Itp-r83Aka1091/Itp-r83Aug3 mutants at 17.5[o]C. The wing posture defect found in these mutants when grown at 25[o]C is also suppressed to a significant extent.

Overexpression of olf186-FScer\UAS.cZa in wild-type neurons (under the control of Scer\GAL4elav-C155) does not afffect SOCE and '[Ca[2+]'][[ER]], although it does elevate '[Ca[2+]'][[i]] to ~1υM in wild-type and Itp-r83Aka1091/Itp-r83Aug3 backgrounds.

Ca-P60AKum170/olf186-FEY01467; Itp-r83Aka1091/Itp-r83Aug3 flies exhibit normal wings and normal levels of spontaneous electrical activity in DLM recordings. Flight ability is restored in a significant number of these triple mutant flies. This is in contrast to the complete loss of flight ability in Itp-r83Aka1091/Itp-r83Aug3 mutants and in olf186-FEY01467/+; Itp-r83Aka1091/Itp-r83Aug3 or Ca-P60AKum170/+; Itp-r83Aka1091/Itp-r83Aug3 mutants. Over 60% of olf186-Fk11505/Ca-P60AKum170; Itp-r83Aka1091/Itp-r83Aug3 adults and approximately 50% of olf186-FEY01467/Ca-P60AKum170; Itp-r83Aka1091/Itp-r83Aug3 adults pass as 'fliers' in the cylinder drop test assay. Air-puff delivery elicited sustainable rhythmic flight patterns similar to wild-type in a high proportion of these flies.

The presence of Ca-P60AKum170 has no effect on Ca[2+] release through the InsP[[3]]R on carbachol stimulation in Itp-r83Aka1091/Itp-r83Aug3 mutants.

The presence of olf186-FEY01467 in either olf186-FEY01467/+; Itp-r83Aka1091/Itp-r83Aug3 or olf186-FEY01467/Ca-P60AKum170; Itp-r83Aka1091/Itp-r83Aug3 organisms restored carbachol-stimulated Ca[2+] release to wild-type levels.

The abnormal wing posture phenotype of Itp-r83Aka1091/Itp-r83Aug3 animals raised at 25'C is suppressed by Ca-P60AKum170/+. Lethality due to Itp-r83Aka1091/Itp-r83Aug3 in animals raised at 17'C is also suppressed by Ca-P60AKum170/+. The resulting animals have the same abnormal wing posture phenotype as Itp-r83Aka1091/Itp-r83Aug3 animals raised at 25'C.

Xenogenetic Interactions
Statement
Reference

Itp-r83Aug3 partially suppresses the climbing defect of 15-day old Scer\GAL4D42>Hsap\TARDBPScer\UAS.cHa flies.

Itp-r83Aug3 extends the median survival of Scer\GAL4D42>Hsap\TARDBPScer\UAS.cHa flies by 6.5 days. Itp-r83Aug3 does not extend the lifespan of wild-type flies.

Complementation and Rescue Data
Partially complements
Comments

Expression of Itp-r83AScer\UAS.cVa in the insulin-producing cells under the control of Scer\GAL4Ilp2.PR rescues the starvation resistance seen in itgr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant flies to wild type levels. The lipid level defects in the fat body cells of starved flies is also rescued, as is the increase in body weight and TAG level. Expression in the fat body under the control of Scer\GAL4c729 partially rescues the starvation resistance phenotype, increase in body weight and abdominal TAG level.

Expression of Itp-r83AScer\UAS.cVa in the insulin-producing cells under the control of Scer\GAL4Ilp2.PR partially restores the profile of TAGs and their constituent fatty acids in Itp-r83Aka1091/Itp-r83Aug3 mutants close to that of the wild type under starvation.

Expression of Itp-r83AScer\UAS.cVa in the insulin-producing cells under the control of Scer\GAL4Ilp2.PR suppresses the overeating seen in itgr[ku] (Itp-r83Aka1091/Itp-r83Aug3) mutant females.

Complete rescue of the altered wing posture is seen in Itp-r83AScer\UAS.cVa; Scer\GAL4Ilp2.PR/+; Itp-r83Aka1091/Itp-r83Aug3 animals. Flight ability is also rescued significantly in these flies. The delivery of an air puff stimulus to Itp-r83Aka1091/Itp-r83Aug3 flies expressing Scer\GAL4Ilp2.PR-driven Itp-r83AScer\UAS.cVa leads to rhythmic generation of action potentials similar to what is observed in wild-type flies. However, the response in some flies is more erratic and could not be maintained for more than five seconds.

Complete rescue of the altered wing posture is seen in Itp-r83AScer\UAS.cVa; Scer\GAL4Ilp2.PR/+; Itp-r83Awc703/Itp-r83Aug3 animals. Flight ability is also rescued significantly in these flies. The delivery of an air puff stimulus to Itp-r83Awc703/Itp-r83Aug3 flies expressing Scer\GAL4Ilp2.PR-driven Itp-r83AScer\UAS.cVa leads to rhythmic generation of action potentials, but in most flies the air puff response lasts for a shorter period of time compared with the control flies.

Wing posture and air puff-induced flight (assessed in single fly tethered assays) are not rescued when Itp-r83AScer\UAS.cVa; Scer\GAL4Ilp2.PR/Scer\GAL80[ts.αTub84B]; Itp-r83Aka1091/Itp-r83Aug3 animals are grown at 19[o]C during pupal and adult stages, but are completely rescued when these animals are grown at 30[o]C. Itp-r83AScer\UAS.cVa; Scer\GAL4Ilp2.PR/Scer\GAL80[ts.αTub84B]; Itp-r83Aka1091/Itp-r83Aug3 organisms grown at 30[o]C during pupal stages, but shifted to 19[o]C as adults, have normal wing posture and air puff-induced flight.

Expression of Itp-r83AScer\UAS.cVa under the control of Scer\GAL4Ilp2.PR in Itp-r83Asv35/Itp-r83Aug3 mutant larvae significantly rescues reduced larval body size. Approximately half the surviving larvae can pupate and emerge as adults.

Expression of Itp-r83AScer\UAS.cVa under the control of Scer\GAL4Ddc.PL in Itp-r83Asv35/Itp-r83Aug3 mutant larvae significantly rescues reduced larval body size and lethality.

Expression of Itp-r83AScer\UAS.cVa under the control of Scer\GAL4Ddc.PL and Scer\GAL4Ilp2.PR in Itp-r83Asv35/Itp-r83Aug3 mutant larvae rescues body size and lethality. Survival is not improved beyond that observed with over-expression under the control of only Scer\GAL4Ddc.PL alone.

Defective feeding behaviour in Itp-r83Asv35/Itp-r83Aug3 larvae can be rescued by expression of Itp-r83AScer\UAS.cVa under the ontrol of Scer\GAL4Ilp2.PR or Scer\GAL4Ddc.PL.

Rescue of Itp-r83Awc703/Itp-r83Aug3 flies by expression of Itp-r83AScer\UAS.cVa under the control of Scer\GAL4hs.PB following a heat shock shows that expression during early pupal development is sufficient to rescue flight behavior and physiology, while expression after adult emergence is ineffective in rescuing flight.

Expression of Itp-r83AScer\UAS.cVa under the control of Scer\GAL4hs.PB rescues flightlessness in 30% of Itp-r83Asa54/Itp-r83Aug3 flies; the remaining flies still show crumples wing margins.

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Synonyms and Secondary IDs (6)
References (19)