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General Information
Symbol
Dmel\mlenap-ts1
Species
D. melanogaster
Name
FlyBase ID
FBal0023798
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
napts, napts1, mlenapts
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
point mutation
Nucleotide change:

C5978346G

Amino acid change:

T415S | mle-PA; T58S | mle-PC

Comment:

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

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

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).

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 ( 0 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

mlenap-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. mlenap-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 mlenap-ts1 produce significantly fewer eggs than wild-type controls and aging homozygous mutants display premature neurodegeneration (their brains frequently contain vacuoles).

mlenap-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 mlenap-ts1 mutants is further worsened in adult flies aged at either low or high temperature.

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

mlenap-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.

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

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

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 mlenap-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.

The electrocardiogram (EKG) of mlenap-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).

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.

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

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

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

Mutation induces arrhythmia in the heartbeat of larvae at temperatures above 20oC; heartbeat becomes normally rhythmic again after a shift back to 20oC. 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.

Homozygous larvae raised at the restrictive temperature (37oC 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 tipEunspecified. Embryos raised at 18oC or 34oC 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.

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.

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) mlenap-ts1 mutant flies. Stimulation of the giant fibre (GF) sometimes fails to evoke DLM potentials following the buzz.

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

Amount of para product is reduced in mlenap-ts1 mutants.

parats1 mlenap-ts1 double mutant bristle sensory cells in small-patch mosaic flies have normal branching and terminal arborisation patterns in the central nervous system.

Double mutants with mlenap-ts1 or parats1 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.

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 eag4PM Sh21 or eag1 Sh21 flies.

Paralysis when homozygous.

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

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

The temperature at which mutant flies become paralysed is dependent on the rearing temperature; flies raised at a low temperature (8oC) become paralysed at a lower temperature than flies raised at a high (30oC) temperature. Temperatures up to 7oC 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.

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

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.

Neurotoxin sensitive.

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

Shows unconditional lethality when double mutant with parats1. Lethality is evident even when the flies are grown at 18oC. Lethality acts before pupation.

Flies are paralysed above 34oC.

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

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

Homozygous mlenap-ts1 flies paralyzed at lower temperature than hemizygous mlenap-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 parats1

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

mlenap-ts1 is a non-suppressor of neuroanatomy defective phenotype of slo1

mlenap-ts1 is a non-suppressor of neuroanatomy defective phenotype of slo98

Other
Phenotype Manifest In
Enhanced by
Statement
Reference

mlenap-ts1 has phenotype, enhanceable by Khc4

mlenap-ts1 has phenotype, enhanceable by Khc5

Suppressed by
Statement
Reference

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

Suppressor of
Statement
Reference

mlenap-ts1 is a suppressor of NMJ bouton | supernumerary phenotype of sei2

mlenap-ts1 is a suppressor of neuromuscular junction phenotype of sei2

NOT Suppressor of
Statement
Reference

mlenap-ts1 is a non-suppressor of NMJ bouton | supernumerary phenotype of slo1

mlenap-ts1 is a non-suppressor of neuromuscular junction phenotype of slo1

mlenap-ts1 is a non-suppressor of NMJ bouton | supernumerary phenotype of slo98

mlenap-ts1 is a non-suppressor of neuromuscular junction phenotype of slo98

Other
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 mlenap-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.

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

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

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.

The reduced locomotor activity seen in mlenap-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).

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

mlenap-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 mlenap-ts1 sdaiso6.10 double mutant flies is similar to that seen in mlenap-ts1 single mutants.

The threshold for activation of the giant fiber in bss1 mlenap-ts1 and sdaiso6.10 mlenap-ts1 animals following single stimulus pulses (0.2ms duration, 0.5Hz) is elevated compared to wild type.

mlenap-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.

Flies that are also Khc6/KhcBD show synthetic lethality.

shi and comt alleles show no lethal interaction with mlenap-ts1.

Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Rescued by
Comments

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

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

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

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

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

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

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (8)
References (52)