FlyBase Allele Report: Dmel\mle[nap-ts1]

General Information

Symbol

Dmel\mle^nap-ts1

Species

D. melanogaster

Name

FlyBase ID

FBal0023798

Feature type

allele

Associated gene

Dmel\mle

Associated Insertion(s)

Carried in Construct

Also Known As

nap^ts, nap^ts1, mle^napts

Key Links

Genomic Maps

JBrowse

Allele class

heat sensitive gain of function allele

Mutagen

ethyl methanesulfonate

Nature of the Allele

Allele class

heat sensitive gain of function allele

(Kernan et al., 1991)

Mutagen

ethyl methanesulfonate

(Kernan et al., 1991, Budnik et al., 1990)

Progenitor genotype

Cytology

Description

Nucleotide substitution: C1664G. Amino acid replacement: T415S. Also carries a net insertion of 6bp (replacement of 1bp with a 7bp insert) within an intron (this change is not responsible for the mutant phenotype).

(Kernan et al., 1991)

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

2R:5,978,346..5,978,346 [-]

Nucleotide change:

C5978346G

Amino acid change:

T415S | mle-PA; T58S | mle-PC

Comment:

The same nucleotide change is observed in mle^nap-ts2, mle^nap-ts3, mle^nap-ts4, and mle^nap-ts5. A 6bp insertion in an intron is also present in each of these strains but that is not likely to cause the phenotype.

(Kernan et al., 1991)

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

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

model of epilepsy

CEA

(Fergestad et al., 2006)

Modifiers Based on Experimental Evidence ( 0 )

Disease

Interaction

References

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal behavior

(Cowan and Siegel, 1984)

abnormal behavior | recessive | heat sensitive

(Hurd et al., 1996, Kernan et al., 1991, Stern et al., 1990, Ganetzky, 1984)

abnormal locomotor behavior | third instar larval stage

(Lnenicka et al., 2003)

abnormal neuroanatomy | adult stage

(Garber et al., 2012)

abnormal neuroanatomy | heat sensitive

(Zhong and Wu, 2004)

abnormal neuroanatomy | third instar larval stage

(Lnenicka et al., 2003)

abnormal neurophysiology

(Kuebler et al., 2001, Pavlidis and Tanouye, 1995, Engel and Wu, 1992)

abnormal neurophysiology | heat sensitive

(Nelson and Wyman, 1990)

abnormal neurophysiology | recessive | heat sensitive

(Jarecki and Keshishian, 1995)

abnormal song | recessive

(Peixoto and Hall, 1998)

chemical resistant

(Bloomquist et al., 1989)

chemical sensitive

(Wang et al., 2000)

chemical sensitive | heat sensitive

(Sakai et al., 1989)

chemical sensitive | partially | recessive

(Leibovitch et al., 1995)

female semi-sterile

(Garber et al., 2012)

lethal | temperature conditional

(Garber et al., 2012)

paralytic

(Chandrashekaran and Sarla, 1993)

paralytic | heat sensitive

(Jarecki and Keshishian, 1995, Pavlidis and Tanouye, 1995, Budnik et al., 1990, Elkins and Ganetzky, 1990, Nelson and Wyman, 1990, Jackson et al., 1984)

paralytic | recessive | heat sensitive

(Reenan and Rogina, 2008, Hall et al., 1982)

paralytic | temperature conditional

(Garber et al., 2012)

partially lethal

(Garber et al., 2012)

short lived

(Fergestad et al., 2006)

short lived | recessive | heat sensitive

(Reenan and Rogina, 2008)

short lived | temperature conditional

(Garber et al., 2012)

Phenotype Manifest In

adult brain

(Garber et al., 2012, Fergestad et al., 2006)

axon & motor neuron | conditional ts

(Zhong and Wu, 2004)

embryonic/larval heart | heat sensitive

(Dowse et al., 1995)

embryonic/larval neuromuscular junction

(Lnenicka et al., 2003)

giant fiber neuron

(Kuebler et al., 2001)

neuromuscular junction & synapse | conditional ts

(Jarecki and Keshishian, 1995)

NMJ bouton

(Lnenicka et al., 2003)

synapse | ectopic | heat sensitive

(Jarecki and Keshishian, 1995)

Detailed Description

Statement

Reference

mle^nap-ts1 homozygous flies are lethal at either 18[o]C or 29[o]C and their eclosion rate is significantly reduced also at 25[o]C. mle^nap-ts1 mutants are especially sensitive to temperature manipulations during the embryonic development as only few escapers or no adults at all manage to eclose when the animals are kept at either 18[o]C or 29[o]C during the first day after egg laying before transferring to 25[o]C for the rest of the development. Females homozygous or heterozygous for mle^nap-ts1 produce significantly fewer eggs than wild-type controls and aging homozygous mutants display premature neurodegeneration (their brains frequently contain vacuoles).

mle^nap-ts1 mutant adults are more sensitive to paralysis at high temperatures compared to controls and this sensitivity depends on the temperature the flies have been kept in after eclosion: the penetrance of the paralytic phenotype is higher in mutant flies kept at either 18[o]C or 29[o]C compared to those kept at 25[o]C. Similarly, the short lived phenotype of mle^nap-ts1 mutants is further worsened in adult flies aged at either low or high temperature.

(Garber et al., 2012)

Homozygous mle^nap-ts1 mutants display higher sensitivity to the paralysing effects of elevated temperatures at a younger age than do mle^nap-ts1/+ heterozygotes or wild-type flies. Homozygous mle^nap-ts1 mutant flies have shortened lifespan compared to controls.

(Reenan and Rogina, 2008)

mle^nap-ts1/Y males are significantly more sensitive to isoflurane than control flies; the latency between nerve shock and excitatory junctional potential onset at the neuromuscular junction treated is significantly larger in the mutant flies than in controls following treatment with isoflurane.

(Sandstrom, 2008)

mle^nap-ts1 flies have a significantly shortened lifespan and show mild neuropathology with multiple regions of vacuolization present in most brain sections.

(Fergestad et al., 2006)

mle^nap-ts1 larvae fail to show the temperature-induced enhancement of arborization at motor axon terminals seen when wild-type larvae are raised at 30^oC. When reared at room temperature, the extent of arborization is similar between mle^nap-ts1 and wild-type larvae.

(Zhong and Wu, 2004)

The rate of locomotion is significantly reduced in mutant larvae compared to controls.

The terminals of axon 1 (which innervates muscles 6 and 7) are thinner in mle^nap-ts1 larvae compared to wild type. The terminal area is significantly smaller in the mutants compared to wild type, although terminal length, branch number and bouton number are not significantly affected. The distribution of bouton widths is shifted to smaller value in mutant larvae.

(Lnenicka et al., 2003)

The electrocardiogram (EKG) of mle^nap-ts1 pupal hearts is irregular, usually showing small extra peaks scattered throughout the record. The voltage in the EKG is universally much lower than normal. Injection of norepinephrine does not accelerate the heart rate (in contrast to wild type).

(Johnson et al., 2001)

The seizure threshold following short wavetrains of high-frequency electrical stimuli is increased in mutant flies compared to controls; seizures cannot be evoked with the standard 300ms high-frequency stimuli at 100V, but can be evoked using 400ms high-frequency stimuli. Under these conditions, the seizure threshold of the mutant flies is 72.2 +/- 7.3 V.

The threshold for activation of the giant fiber in mutant animals following single stimulus pulses (0.2ms duration, 0.5Hz) is elevated compared to wild type.

The giant fiber following frequency (the maximum stimulation frequency that the giant fiber pathway can reliably follow) is greatly reduced compared to wild type in mutant animals.

(Kuebler et al., 2001)

When exposed to 10mM paraquat for 48hr, mutants show 28% survival (wild type shows 97% survival).

(Wang et al., 2000)

The courtship song parameters cycles per pulse, amplitude of sound and interpulse frequency are normal in homozygous males at 25^oC, but the interpulse interval is significantly longer than in wild-type males at 25^oC.

(Peixoto and Hall, 1998)

Temperature sensitive paralysis threshold is 36^oC. Flies become paralysed within 15 seconds of a temperature shift to 39^oC and recover completely within 15 seconds of shifting back to room temperature.

(Hurd et al., 1996)

Mutation induces arrhythmia in the heartbeat of larvae at temperatures above 20^oC; heartbeat becomes normally rhythmic again after a shift back to 20^oC. Mutation also reduces the temperature-sensitivity of heart rate over a wide range of temperatures. Mutation acts indirectly on action potentials through the para gene, adults exhibit reversible paralysis.

(Dowse et al., 1995)

Homozygous larvae raised at the restrictive temperature (37^oC for 6 hours/day from late embryogenesis through to third larval instar) show an increased frequency of ectopic neuromuscular synapses. This frequency is increased further if the larvae are also mutant for tipE^unspecified. Embryos raised at 18^oC or 34^oC show an increased frequency of immature filopodial contacts on muscle fibres 6 and 7 ("collateral sprouts") compared to wild-type embryos raised at the same temperature.

(Jarecki and Keshishian, 1995)

Heterozygotes and homozygotes show increased sensitivity to halothane and chloroform, but not to trichloroethylene in an inebriometer assay (an assay of geotactic and postural behaviour) compared to wild-type flies. Homozygotes are more sensitive than heterozygotes. Decapitated flies lose the halothane sensitive phenotype.

(Leibovitch et al., 1995)

The delivery of an electrical buzz (50-400 msec) to the brain does not cause abnormal spontaneous activity ("seizures") in the dorsal longitudinal muscle (DLM) mle^nap-ts1 mutant flies. Stimulation of the giant fibre (GF) sometimes fails to evoke DLM potentials following the buzz.

(Pavlidis and Tanouye, 1995)

para mutant olfactory, viability and paralytic phenotypes with are enhanced in a mle^nap-ts1 background.

(Lilly et al., 1994)

Amount of para product is reduced in mle^nap-ts1 mutants.

(Amichot et al., 1993)

para^ts1 mle^nap-ts1 double mutant bristle sensory cells in small-patch mosaic flies have normal branching and terminal arborisation patterns in the central nervous system.

(Burg et al., 1993)

Double mutants with mle^nap-ts1 or para^ts1 show no exaggeration of the paralytic phenotypes, nor any efect on their viability and fertility. These results suggest stmA does not interact with para or mle.

(Chandrashekaran and Sarla, 1993)

Increases the latency and refractory period and lowers the following frequency of the giant fibre response of the tergotrochanteral muscle pathway, but does not affect the dorsal longitudinal muscle pathway. Suppresses the spontaneous activity of the dorsal longitudinal and dorsoventral indirect flight muscles seen at rest in eag^4PM Sh²¹ or eag¹ Sh²¹ flies.

(Engel and Wu, 1992)

Paralysis when homozygous.

(Kernan et al., 1991)

Flies become paralysed at 37^oC. This paralysis is suppressed by Dp(1;4)r⁺l.

(Budnik et al., 1990)

Flies become paralysed at 35-37^oC. The long-latency response of the dorsal longitudinal muscle disappears abruptly as the temperature is increased to 35 +/- 1^oC, although the short-latency response is normal. The long-latency response returns if the temperature is lowered. tipE^unspecified mle^nap-ts1 double mutant flies become paralysed at 31-32^oC. The long-latency response of the dorsal longitudinal muscle disappears abruptly as the temperature is increased to 31 +/- 2^oC, although the short-latency response is normal.

(Elkins and Ganetzky, 1990)

The temperature at which mutant flies become paralysed is dependent on the rearing temperature; flies raised at a low temperature (8^oC) become paralysed at a lower temperature than flies raised at a high (30^oC) temperature. Temperatures up to 7^oC above the paralytic temperature do not block the dorsal longitudinal muscle (DLM) response to giant fibre stimulation. The jump muscle response is variable at this high temperature, some flies have a normal response, some have no response at all, and some have a reduced amplitude response. The interval from brain stimulation of the giant fibre to a response in the DLM or jump muscle is longer than in wild-type flies at all temperatures. Both the DLM and the jump muscle have a weaker following frequency than wild-type, which can be rescued by injecting 4-aminopyridine into mutant flies.

(Nelson and Wyman, 1990)

Homozygous flies are rapidly paralysed at the restrictive temperature of 37.5^oC. This phenotype is suppressed by Dp(1;4)r⁺l.

(Stern et al., 1990)

Flies show a threefold resistance to deltamethrin at the LC₅₀ level compared to wild-type. The onset of intoxication by deltamethrin, fenfluthrin, MTI-800 or NDRC 157 is delayed compared to wild-type. Dorsolongitudinal flight muscles treated with fenfluthrin show longer latencies to the appearance of spontaneous activity and an absence or reduction of burst discharges compared to wild-type.

(Bloomquist et al., 1989)

Neurotoxin sensitive.

(Sakai et al., 1989)

mle^nap-ts1 males show conditioning of courtship behaviour, but retention of the conditioned response is abnormally short. Sh⁵ mle^nap-ts1 double mutant males are essentially normal in their acquisition of conditioned courtship behaviour, but are defective in retention of the conditioned response.

(Cowan and Siegel, 1984)

Shows unconditional lethality when double mutant with para^ts1. Lethality is evident even when the flies are grown at 18^oC. Lethality acts before pupation.

(Ganetzky, 1984)

Flies are paralysed above 34^oC.

(Jackson et al., 1984)

Dissociated central nervous system cultures from mle^nap-ts1 larvae appear morphologically normal and cells have a similar survival rate to wild-type at both 22^oC and at the restrictive temperature of 35^oC. mle^nap-ts1 cell cultures show a significantly higher resistance to veratridine than wild-type cells at 22^oC and 35^oC.

(Suzuki and Wu, 1984)

Homozygotes show normal locomotor behaviour at the permissive temperature (21^oC), but both larvae and adults rapidly become paralysed at 37^oC, in contrast to wild-type. Mutant flies have fewer saxitoxin-binding sites than wild-type, but the K_d and pH sensitivity of saxitoxin binding and the effects of temperature on saxitoxin binding are the same as wild-type.

(Hall et al., 1982)

Homozygous mle^nap-ts1 flies paralyzed at lower temperature than hemizygous mle^nap-ts1/mle^- flies (Kernan and Ganetzky). Paralysis of homozygotes suppressed by para⁺ duplications (Stern, Kreber and Ganetzky, 1990). temperature-sensitive paralysis when homo- or hemizygous; male viable when homozygous; lethal with para^ts1

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Suppressed by

Statement

Reference

mle^nap-ts1 has partially lethal phenotype, suppressible by Dp(1;4)r⁺l

(Garber et al., 2012)

mle^nap-ts1 has lethal | temperature conditional phenotype, suppressible by Dp(1;4)r⁺l

(Garber et al., 2012)

mle^nap-ts1 has abnormal neuroanatomy | adult stage phenotype, suppressible by Dp(1;4)r⁺l

(Garber et al., 2012)

mle^nap-ts1 has abnormal locomotor behavior | third instar larval stage phenotype, suppressible by Dp(1;4)r⁺l

(Lnenicka et al., 2003)

Enhancer of

Statement

Reference

mle^nap-ts1 is an enhancer of abnormal song | recessive phenotype of cac¹

(Peixoto and Hall, 1998)

Suppressor of

Statement

Reference

mle^nap-ts1 is a suppressor of abnormal neuroanatomy phenotype of sei²

(Lee and Wu, 2010)

para^JS1, mle^nap-ts1, para[+] is a suppressor of bang sensitive | recessive phenotype of eas²

(Song and Tanouye, 2007)

mle^nap-ts1 is a suppressor of uncoordinated | RU486 conditional phenotype of Scer\GAL4^{elav.Switch.PO}, Sh^{DN.EKI.UAS.GFP(GL)}

(Mosca et al., 2005)

mle^nap-ts1 is a suppressor of increased rate of movement | RU486 conditional phenotype of Scer\GAL4^{elav.Switch.PO}, Sh^{DN.EKI.UAS.GFP(GL)}

(Mosca et al., 2005)

mle^nap-ts1 is a suppressor of abnormal neurophysiology phenotype of para^bss1

(Kuebler et al., 2001)

mle^nap-ts1 is a suppressor | partially of chemical sensitive phenotype of Sh²¹, eag¹

(Wang et al., 2000)

mle^nap-ts1 is a suppressor of abnormal song | recessive phenotype of cac¹

(Peixoto and Hall, 1998)

NOT Suppressor of

Statement

Reference

mle^nap-ts1 is a non-suppressor of abnormal neuroanatomy phenotype of slo⁹⁸

(Lee and Wu, 2010)

mle^nap-ts1 is a non-suppressor of abnormal neuroanatomy phenotype of slo¹

(Lee and Wu, 2010)

Other

Statement

Reference

mle^nap-ts1, para^bss1 has abnormal neurophysiology phenotype

(Kuebler et al., 2001)

jus^iso6.10, mle^nap-ts1 has abnormal neurophysiology phenotype

(Kuebler et al., 2001)

Khc⁶/Khc^BD, mle^nap-ts1 has lethal phenotype

(Hurd et al., 1996)

mle^nap-ts1, para^ts1 has paralytic | heat sensitive phenotype

(Dowse et al., 1995)

mle^nap-ts1, para^ts1 has lethal phenotype

(Ganetzky, 1984)

mle^nap-ts1, para^ts1 has lethal | recessive phenotype

(Ganetzky, 1984)

mle^nap-ts1, para^ts1 has abnormal behavior | dominant phenotype

(Ganetzky, 1984)

mle^nap-ts1, para^ts115 has partially lethal phenotype

(Ganetzky, 1984)

mle^nap-ts1, para^ts115 has lethal | heat sensitive phenotype

(Ganetzky, 1984)

mle^nap-ts1, para^lk5 has lethal | dominant phenotype

(Ganetzky, 1984)

Phenotype Manifest In

Enhanced by

Statement

Reference

mle^nap-ts1 has phenotype, enhanceable by Khc⁴

(Hurd et al., 1996)

mle^nap-ts1 has phenotype, enhanceable by Khc⁵

(Hurd et al., 1996)

Suppressed by

Statement

Reference

mle^nap-ts1 has adult brain phenotype, suppressible by Dp(1;4)r⁺l

(Garber et al., 2012)

Suppressor of

Statement

Reference

mle^nap-ts1 is a suppressor of NMJ bouton | increased number phenotype of sei²

(Lee and Wu, 2010)

mle^nap-ts1 is a suppressor of neuromuscular junction phenotype of sei²

(Lee and Wu, 2010)

NOT Suppressor of

Statement

Reference

mle^nap-ts1 is a non-suppressor of NMJ bouton | increased number phenotype of slo⁹⁸

(Lee and Wu, 2010)

mle^nap-ts1 is a non-suppressor of neuromuscular junction phenotype of slo⁹⁸

(Lee and Wu, 2010)

mle^nap-ts1 is a non-suppressor of NMJ bouton | increased number phenotype of slo¹

(Lee and Wu, 2010)

mle^nap-ts1 is a non-suppressor of neuromuscular junction phenotype of slo¹

(Lee and Wu, 2010)

Other

Statement

Reference

mle^nap-ts1, para^bss1 has giant fiber neuron phenotype

(Kuebler et al., 2001)

jus^iso6.10, mle^nap-ts1 has giant fiber neuron phenotype

(Kuebler et al., 2001)

Additional Comments

Genetic Interactions

Statement

Reference

The reduced viability (at 25[o]C) or complete lethality (at either 18[o] or 25[o]C) of mle^nap-ts1 homozygous mutants as well as the increased neurodegeneration in aging mutant adults can be partially rescued by combination with Dp(1;4)r⁺l.

(Garber et al., 2012)

A mle^nap-ts1 mutant background suppresses synaptic satellite growth, particularly type M satellite growth, in mle^nap-ts1; sei² mutants.

A mle^nap-ts1 mutant background does not affect synaptic satellite growth in slo¹ or slo⁹⁸ mutants.

(Lee and Wu, 2010)

para^JS1/+; mle^nap-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.

(Song and Tanouye, 2007)

The reduced locomotor activity seen in mle^nap-ts1 larvae is restored if the larvae also carry Dp(1;4)r⁺l (the double mutant larvae have locomotor activity greater than that of controls).

(Lnenicka et al., 2003)

shi¹/Y ; mle^nap-ts1/mle^nap-ts1 animals have near-normal heartbeats at temperatures from 20-35^oC, but have an abnormal heart rate at 37^oC. shi¹/Y ; mle^nap-ts1/+ animals have near-normal heartbeats at temperatures from 25-37^oC, but have an abnormal heart rate at 20^oC. shi¹/shi¹ ; mle^nap-ts1/mle^nap-ts1 animals have significantly slower than normal heart rates at all temperatures but the beat is normally rhythmic. shi¹/shi¹ ; mle^nap-ts1/+ animals have significantly slower and less rhythmic than normal heart rates at several temperatures.

(Johnson et al., 2001)

mle^nap-ts1 suppresses the reduced seizure threshold of bss¹ flies following high-frequency electrical stimuli, raising the seizure threshold to wild-type levels in the double mutant flies.

The seizure threshold following high-frequency electrical stimuli of mle^nap-ts1 sda^iso6.10 double mutant flies is similar to that seen in mle^nap-ts1 single mutants.

The threshold for activation of the giant fiber in bss¹ mle^nap-ts1 and sda^iso6.10 mle^nap-ts1 animals following single stimulus pulses (0.2ms duration, 0.5Hz) is elevated compared to wild type.

(Kuebler et al., 2001)

mle^nap-ts1 seems to enhance the interpulse interval defects of cac¹ males, but partly suppresses the cac¹ defects in cycles per pulse and amplitude of sound.

(Peixoto and Hall, 1998)

Flies that are also Khc⁶/Khc^BD show synthetic lethality.

(Hurd et al., 1996)

shi and comt alleles show no lethal interaction with mle^nap-ts1.

(Ganetzky, 1984)

Xenogenetic Interactions

Statement

Reference

Complementation and Rescue Data

Rescued by

mle^nap-ts1 is rescued by mle^+t10.5

(Dowse et al., 1995)

Comments

Dp(1;4)r⁺l complements the recessive life-span and paralysis phenotypes of mle^nap-ts1.

(Reenan and Rogina, 2008)

Mutant phenotype can be rescued by P element mediated transformation of a wild type mle gene copy.

(Kernan et al., 1991)

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

Comments

mle^nap-ts1 suppresses phenotypes of Sh, Hk, bas, bss, eas, kdn and tko mutants. Suppression is recessive and occurs at temperatures permissive for mle^nap-ts1, and is indirect and function-specific, rather than allele-specific.

(Ganetzky and Wu, 1982)

The number of saxitoxin binding sites is reduced by about 40% in the mutant relative to wild-type.

(Jackson et al., 1984)

The analysis of saxitoxin binding suggests that there are no structural differences between the sodium channels of mle^nap-ts1 and wild-type flies, but that there are a reduced number of sodium channels in the mutant flies.

(Hall et al., 1982)

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (8)

Reported As

Symbol Synonym

mle^nap-ts1

(Sandstrom, 2008, Song and Tanouye, 2007)

mle^nap

(Baker et al., 1994)

mle^napts1

(Pavlidis and Tanouye, 1995)

mle^napts

(Garber et al., 2012, Reenan and Rogina, 2008, Fergestad et al., 2006, Gerber and Keller, 2001, Kuebler et al., 2001, Reenan et al., 2000, Seeburg, 2000)

nap^TS

(Akbergenova et al., 2018)

nap^ts1

(Fergestad et al., 2006, Johnson et al., 2001, Wang et al., 2000, Peixoto and Hall, 1998, Leibovitch et al., 1995, Kernan et al., 1991)

napts

(Lee and Wu, 2002)

Name Synonyms

Secondary FlyBase IDs

FBal0032154

References (53)

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