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General Information
Symbol
Dmel\eas2
Species
D. melanogaster
Name
FlyBase ID
FBal0003489
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
easPC80
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

2bp deletion at nucleotide position 1004-1005, causing a frameshift mutation, which introduces a stop codon at nucleotide position 1078. Predicted protein would have the first 260 amino acids of the eas product, and lack the conserved kinase domain.

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 )
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
model of  epilepsy
is ameliorated by shi1
is ameliorated by Top1112
is ameliorated by Top1JS
is ameliorated by Mmp1f1.UAS
is ameliorated by SREBP52
is ameliorated by ACCB131
is ameliorated by FASN1KK107330
is ameliorated by SREBP189
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

eas2/eas2 flies are bang sensitive and have a low seizure threshold in response to high frequency stimulation (similar at room temperature or after brief heat shock).

eas2/eas2 mutants are bang sensitive; exhibit defects in synaptic transmission, as shown by significantly reduced response rate to GF circuit stimulation at 100 Hz; and like wild type flies they do not exhibit spontaneous seizure activity or loss of GF circuit response during temperature shift to 30[o]C.

Hemizygous eas2 flies are bang sensitive.

When subjected to mechanical shock for 10 seconds, eas2 mutant flies undergo robust seizure activity and paralysis, with a mean recovery time of ~80 seconds, compared to ~10 seconds in controls.

Mutant hearts show a significant reduction in the average heartbeat length (heart period) compared to wild type, due to decreased diastolic and systolic intervals. The mutant hearts are more constricted than wild type. The mutant hearts do not show a change in fractional shortening, but the absolute volume output of the heart s dramatically reduced (by approximately 40%) compared to wild type. The ventral longitudinal myofibrils show severe degeneration and disorganization in the mutant hearts, and to a lesser extent, the inner transverse myofibrils are also affected.

eas2/easKG01772 adults have an increased tendency to have a faster heart rate and a significantly constricted heart tube.

Upon being subjected to pacing-induced stress, mutant flies show elevated incidences of heart failure compared to control flies at both young (1 and 2 week) and old (4 week) ages.

1 week old mutant females show a nearly 50% increase in whole fly triglyceride levels compared to wild type. The triglyceride levels in the hearts of these animals are increased by 20% compared to controls.

Mean recovery time from bang sensitive paralysis following a mechanical shock is approximately 81 seconds in hemizygous males.

Seizure-like electrical activity in the motoneurons can be elicited in mutant flies with a high-frequency stimulus. After this initial seizure, there is a "synaptic failure" period where the giant fibre system neural circuit fails to drive muscle potentials in the dorsal longitudinal muscle. A final recovery seizure is then observed, followed by restoration of transmission in the giant fibre system shortly thereafter.

1-2 day old eas2 flies require 44.6 +/- 5.6 seconds to recover from paralysis after being subjected to a 10 second vortex. This recovery time increases with age. Mutant flies have a reduced seizure threshold (the minimum voltage required to induce seizure activity in the dorsal longitudinal muscles after a high-frequency stimulus) compared to controls.

Heterozygous females show no bang sensitivity, hemizygous males show 100% bang sensitivity. Mutant flies are more sensitive to seizures than wild-type flies; seizures are induced by a high frequency stimulus of low strength - the mean seizure threshold is 7.6 +/- 1.9V compared to 36.7 +/- 6.5 V for control flies (for a high frequency stimulus of 0.5msec pulses delivered at 200Hz for 300 msec).

eas2 mutants have a range of defects in the mushroom body; 29.6% lack β' and β lobes in both hemispheres, 14.8% lack α' and α vertical lobes in both hemispheres, while >1% possess all five lobes in both hemispheres. The remaining flies have different combinations of mushroom body phenotype in the left and right hemisphere. The γ neurons of the mushroom body appear to be normal in all eas2 mutants. The neuroblasts of eas2 mutants show reduced mitosis in mushroom bodies at the pupal stage. This defect leads to a smaller calyx than in wild-type flies.

Bang-sensitive mutant. Flies usually show abnormal spontaneous activity ("seizures") in the dorsal longitudinal muscle (DLM) and dorsal ventral indirect flight muscle (DVM) lasting approximately 0.5-3 seconds after the delivery of an electrical buzz (50-400 msec) to the brain. Stimulation of the giant fibre (GF) fails to evoke DLM, DVM and tergotrochanteral jump muscle (TTM) potentials following the buzz. This failure lasts for 86 +/- 46 seconds in the DLM. There is a close correlation between the seizure and failure phenotypes; if a seizure occurs, a failure also occurs in greater than 95% of cases, while failures without seizures occurred in approximately 10% of cases. GF evoked responses by the DLM are abnormal during recovery from the buzz. After recovery, there is a refactory period during which a buzz is less effective at inducing seizures and failures. Seizures are not consistently accompanied by failures if the flies are also mutant for mlenap-ts1, and failures which do occur are reduced in duration.

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

Flies become paralyzed when exposed to 10s of vortexing. A brief bang causes a period of hyperactivity lasting 1-2s, during which flies fall over and vigorously flap their wings, shake and bend their legs, and flex their abdomens. The activity rapidly gives way to paralysis. Paralysis is characterized by a relaxed posture of the wings, legs, body and proboscis. After 20-30s, post-paralysis hyperactivity begins, characterized by massive unccordinated motor activity similar to that befoer the paralysis phase. Median time for recovery from the bang is around 110s. There follows a refractory period of 3-5mins. In the giant fibre pathway assay, a stimulus of 200Hz of relatively high voltage for 50-100ms causes 1-2s of intense seizure like activity in the DLMs, followed by no DLM responses (evoked or spontaneous) for an average of 101 +/- 57s. General properties of the giant fibre pathway are normal. Mutant flies show a reduction in PE/PC ratio from the 2.8 of wild type flies to 2.3 for eas2.

Bang sensitive paralytic mutant.

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

eas2 has bang sensitive phenotype, suppressible | partially by Df(3R)MR22/+

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1/mlenap-ts1/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1-Ex1/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1-Ex2/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1-Ex3/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by para[+]/paraJS1-Ex8

eas2 has bang sensitive | recessive phenotype, suppressible | partially by para[+]/paraJS1-Ex6

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1-Ex4/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by para[+]/paraJS1-Ex5

eas2 has bang sensitive | recessive phenotype, suppressible | partially by para[+]/paraJS1-Ex7

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1-Ex9/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by paraJS1-Ex16/para[+]

eas2 has bang sensitive | recessive phenotype, suppressible | partially by Top1JS

NOT suppressed by
Statement
Reference

eas2 has bang sensitive phenotype, non-suppressible by gish[+]/gish04895

eas2 has bang sensitive | recessive phenotype, non-suppressible by paraJS1-Ex10/para[+]

eas2 has bang sensitive | recessive phenotype, non-suppressible by para[+]/paraJS1-Ex11

eas2 has bang sensitive | recessive phenotype, non-suppressible by paraJS1-Ex12/para[+]

eas2 has bang sensitive | recessive phenotype, non-suppressible by paraJS1-Ex14/para[+]

eas2 has bang sensitive | recessive phenotype, non-suppressible by paraJS1-Ex15/para[+]

eas2 has bang sensitive | recessive phenotype, non-suppressible by paraJS1-Ex18/para[+]

eas2 has bang sensitive | recessive phenotype, non-suppressible by eIF4H1EY00852

eas2 has bang sensitive | recessive phenotype, non-suppressible by Top1+t10/Top1JS

eas2 has bang sensitive | recessive phenotype, non-suppressible by Top1JS-EX

eas2 has bang sensitive | recessive phenotype, non-suppressible by Top1G0134/Top1JS

eas2 has bang sensitive | recessive phenotype, non-suppressible by Top1G0201/Top1JS

Enhancer of
Statement
Reference

eas[+]/eas2 is an enhancer of bang sensitive | recessive phenotype of kccDHS1

Other
Phenotype Manifest In
Suppressed by
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference

cacTS2/Y somewhat suppresses bang sensitivity (reduces behavioral paralysis) in eas2/eas2 flies at room temperature; this suppression is increased (to almost 50%) after brief heat shock. After brief heat shock, cacTS2/Y partially suppresses the low seizure threshold in eas2/eas2 flies.

cacJF02572 driven by Scer\GAL4elav-C155 largely suppresses bang sensitivity (reduces behavioral paralysis) in eas2/Y flies at room temperature; driving with Scer\GAL4Gad1.PU or Scer\GAL4ChAT.PU also suppresses the phenotype to a lesser extent.

shi1/shi1 does not rescue the bang sensitive phenotype of eas2/eas2 mutants at 23[o]C, but if incubated for 3 minutes at 26[o]C or 27[o]C immediately before testing, partially rescues the bang sensitive phenotype of eas2/eas2 mutants.

shi1/shi1, eas2/eas2 double mutants exhibit defects in synaptic transmission, as shown by significantly reduced response rate to GF circuit stimulation at 100 Hz; and show seizure-like activity in the DLM and loss of GF circuit responsiveness after temperature shift to 29[o]C.

Expression of shits1.IVS.p10.20xScer\UAS under the control of Scer\GAL4GMR57C10 partially suppresses the bang sensitivity of hemizygous eas2 flies when incubated for 3 min at 28[o]C, but not at 23[o]C.

shits1.IVS.p10.20xScer\UAS under the control of Scer\GAL4RapGAP1-OK6 does not rescue the bang sensitivity of hemizygous eas2 flies temperature shifted to 28[o]C.

shits1.IVS.p10.20xScer\UAS under the control of Scer\GAL4ChAT.PU fully rescues, or under the control of Scer\GAL4shot-OK307 partially rescues the bang sensitivity of hemizygous eas2 flies temperature shifted to 28[o]C.

eas2 mutants expressing shits1.IVS.p10.20xScer\UAS under the control of Scer\GAL4shot-OK307 display synaptic transmission defects and a higher seizure threshold when heated, as compared with controls.

Expression of Rab5Q88L.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab8T22N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab9S26N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab9Q71L.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab30T21N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab30Q66L.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab32T33N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab35S22N.Scer\UAS.T:Avic\GFP-YFP, Rab3T35N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab3Q80L.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab5S43N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab8Q67L.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab23S51N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab23Q96L.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab27T25N.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab27Q74L.Scer\UAS.P\T.T:Avic\GFP-YFP, Rab32Q79L.Scer\UAS.P\T.T:Avic\GFP-YFP, or Rab35Q67L.Scer\UAS.P\T.T:Avic\GFP-YFP under the control of Scer\GAL4GMR57C10 does not rescue the bang sensitivity of eas2 mutants.

Expression of GABA-B-R2GD699 in astrocytes under the control of Scer\GAL4alrm.PD partially suppresses the delayed recovery seen in eas2 mutant flies in response to mechanical shock.

Df(3R)MR22/+ or Df(3R)MR22/tauEP3203 significantly partially suppresses bang-sensitive behavior in eas2/eas2 flies.

The bang sensitive phenotype seen in eas2/+ mutant females is not suppressed by one copy of gish04895. The penetrance and threshold for seizure initiation are similar to in eas2 mutants alone.

The increased whole fly triglyceride levels seen in 1 week old eas2 females are suppressed if they are also carrying either HLH10652/+ or ACCB131/+.

The increased triglyceride levels seen in the hearts of 1 week old eas2 females are suppressed if they are also expressing either CG3523KK107330 or HLH106NTdel.Scer\UAS under the control of Scer\GAL4HCH.Hand.

Expression of ATPCLGD3552 under the control of Scer\GAL4HCH.Hand rescues the increased heartbeat rate and constricted heart phenotypes of eas2 flies.

Expression of CG3523KK107330 under the control of Scer\GAL4HCH.Hand rescues the increased heartbeat rate, constricted heart phenotype and muscle defects of eas2 flies.

Addition of either HLH10652/+ or ACCB131/+ rescues the increased heartbeat rate and constricted heart phenotypes of eas2 flies.

Expression of HLH106NTdel.Scer\UAS under the control of Scer\GAL4HCH.Hand significantly rescues the increased heartbeat rate, constricted heart phenotype and muscle defects of eas2 flies.

Expression of kccScer\UAS.cHb driven by Scer\GAL4c739 significantly suppresses the bang-sensitive paralytic phenotype of eas2 mutants.

paraJS1 dominantly suppresses the bang sensitive phenotype of eas2 homozygotes by 87%. The minimum voltage of high frequency stimulation of the brain required to induce seizure (the seizure threshold) of eas2 homozygotes is raised to almost wild-type levels by paraJS1/+. The same levels of suppression are seen with paraJS1-Ex1/+, paraJS1-Ex2/+, paraJS1-Ex3/+ and paraJS1-Ex8/+. paraJS1-Ex6/+ is a weaker suppressor (bang sensitivity is suppressed by around 70%) as are paraJS1-Ex4/+, paraJS1-Ex5/+, paraJS1-Ex7/+ and paraJS1-Ex9/+. paraJS1-Ex16 is a very weak suppressor (10%) and paraJS1-Ex10, paraJS1-Ex11, paraJS1-Ex12, paraJS1-Ex13, paraJS1-Ex14, paraJS1-Ex15 and paraJS1-Ex18 don't suppress at all.

The suppression of bang sensitivity of and reduced seizure threshold of eas2 homozygotes is itself suppressed by Tp(1;2)r+75c/+.

paraJS1/+; mlenap-ts1/+ completely suppresses the bang sensitive phenotype of eas2 homozygotes and increases the minimum voltage of high frequency stimulation of the brain required to induce seizure to wild-type levels.

Neither para13.5.Scer\UAS; Scer\GAL4elav.PLu nor paraScer\UAS.cGa; Scer\GAL4elav.PLu reduces suppression of bang sensitivity and seizure threshold reduction of eas2 homozygotes by paraJS1/+.

Rbp2EY00852/Y does not suppress bang sensitivity or reduce seizure threshold seen in eas2 homozygotes.

The bang sensitive phenotype and decreased seizure threshold* of eas2 homozygotes are partially suppressed by Top1JS/Y, Top1JS/Top1G0229, Top1JS/Top1112 or Top1JS/Df(1)ED7294 but not by Top1JS/Top1G0201, Top1JS/Top1G0134 or Top1JS/Y; Top1+t10. Top1JS/Y also reduces the time required to recover after seizure in eas2 homozygotes. The partial suppression of the bang sensitive phenotype and decreased seizure threshold* of eas2 homozygotes is itself suppressed by thScer\UAS.cHa, Scer\GAL4elav-C155. (*seizure threshold = voltage of high frequency stimulation required to induce seizures).

No bang sensitivity is seen in kccDHS1/+; eas2/+ transheterozygotes, but 65% of kccDHS1/kccDHS1 ; eas2/+ adults are bang sensitive.

The suppression of bang sensitivity of eas2/Y mutants caused by mei-P2616/mei-P2616 is age dependent, with the strength of the suppression increasing with age; approximately 32% of 1-2 day old double mutant flies show bang sensitivity, but only 1% of 4-5 day old double mutant flies show bang sensitivity. The recovery time of eas2 flies after being subjected to a 10 second vortex is reduced if they are also mutant for mei-P2616; the time needed for recovery is reduced by about 12% in double mutant 1-2 day old bang sensitive flies and is reduced by about 19% in double mutant 2-3 day old bang sensitive flies. The recovery time of bang sensitive eas2 flies after being subjected to a 10 second vortex is reduced if they are also mutant for su(eas)77 or su(eas)1313. The reduced seizure threshold (the minimum voltage required to induce seizure activity in the dorsal longitudinal muscles after a high-frequency stimulus) of eas2 flies is partly suppressed if they are also mutant for mei-P2616, su(eas)77 or su(eas)1313, although the seizure threshold in the double mutant flies is still lower than that of wild-type controls. The increase in seizure threshold in the double mutants is not accompanied by an increase in giant fiber firing threshold.

eas2/+ ; esg35Ce-1/+ or eas2/+ ; Df(2L)osp29/+ double heterozygous females show no bang sensitivity. The suppression of the bang sensitivity of eas2 flies that is seen when esgEP2009 is overexpressed depends on the overexpression occurring in the larval stage. RU486 has been used to drive expression of esgEP2009 under the control of Scer\GAL4elav.Switch.PO at different time points in development (the Scer\GAL4elav.Switch.PO driver only produces active protein in the presence of RU486) in eas2 animals and the bang sensitivity of the resulting adults has been assayed; a reduced level of bang sensitivity (compared to eas2 single mutant flies) is seen if RU486 induction occurs during embryonic and larval stages or during larval and adult stages, whereas little reduction in bang sensitivity is seen if RU486 induction occurs only in the adult stage, and only a slight reduction in bang sensitivity is seen if RU486 induction occurs only in the embryonic stage. The 100% bang sensitivity of eas2/Y flies can be suppressed by expression of esgEP684 under the control of Scer\GAL4elav.PLu (flies have 4% bang sensitivity), Scer\GAL4Cha.7.4 (flies have 88% bang sensitivity) or Scer\GAL4G14 (flies have 78% bang sensitivity), but it not suppressed by expression of esgEP684 under the control of Scer\GAL4OK6. The seizure sensitivity of eas2 flies is partially suppressed by expression of esgEP684 under the control of Scer\GAL4elav.PLu; the mean seizure threshold is raised to 15.5 +/- 5.7 V (for a high frequency stimulus of 0.5msec pulses delivered at 200Hz for 300 msec). The seizure sensitivity of eas2 flies is partially suppressed by expression of esgEP2009 under the control of Scer\GAL4elav.PLu; the mean seizure threshold is raised to 15.5 +/- 6.8 V (for a high frequency stimulus of 0.5msec pulses delivered at 200Hz for 300 msec). The seizure sensitivity of eas2 flies is partially suppressed by expression of esgEP633 under the control of Scer\GAL4elav.PLu; the mean seizure threshold is raised to 13.3 +/- 3.2 V (for a high frequency stimulus of 0.5msec pulses delivered at 200Hz for 300 msec).

Xenogenetic Interactions
Statement
Reference

Expression of Bper\ptxAact.Scer\UAS in astrocytes under the control of Scer\GAL4alrm.PD partially suppresses the delayed recovery seen in eas2 mutant flies in response to mechanical shock.

Complementation and Rescue Data
Comments

Expression of easScer\UAS.cPa under the control of Scer\GAL4HCH.Hand significantly normalises the heart period of eas2 mutant adults, mainly by restoring the diastolic interval to normal levels. In addition, the cardiac chamber appears normal in size in the rescued animals.

Expression of easScer\UAS.cPa under the control of Scer\GAL4HCH.Hand rescues the stress-induced heart failure rates of eas2 adult hearts to normal levels.

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

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

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (4)
References (25)