FB2026_02 , released June 18, 2026
Allele: Dmel\Pgknubian
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General Information
Symbol
Dmel\Pgknubian
Species
D. melanogaster
Name
FlyBase ID
FBal0215567
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
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Nature of the Allele
Progenitor genotype
Cytology
Description

Amino acid replacement: V357E.

Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Nucleotide change:

T2747190A

Reported nucleotide change:

T?A

Amino acid change:

V357E | Pgk-PA; V357E | Pgk-PB; V357E | Pgk-PC; V357E | Pgk-PD; V357E | Pgk-PE

Reported amino acid change:

V357E

Variant Molecular Consequences
Associated Sequence Data
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Protein sequence
 
Expression Data
Reporter Expression
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Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
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Reference

Pgknubian mutants display robust spontaneous action potential spiking in the dorsal longitudinal flight muscles at 38oC, whereas wild-type flies display very little spontaneous activity. The onset of seizure activity in Pgknubian mutants is observed immediately when animals are shifted to 38oC but rapidly subsides within minutes when maintained at 38oC.

Pgknubian mutant second order neurons in the visual system lose the on/off-transients at 38oC, suggesting a defect in synaptic transmission in the visual pathway. Pgknubian mutants require several minutes of exposure to 38oC before the transients disappear. In addition, the recovery of on/off-transients on return to the permissive temperature in Pgknubian animals also show a slow recovery of photoreceptor repolarisation.

Pgknubian animals do not undergo instant paralysis but require several minutes of exposure to 38oC before loss of motor activity. In addition, the recovery in Pgknubian animals is dependent on the length of exposure to 38oC. After several minutes at 38oC the Pgknubian mutants manifest a block of synaptic transmission, as evidenced by the loss of on-/off-transients in the visual system and the beahavioral paralysis.

The ADP/ATP ratio is found to be greatly elevated in Pgknubian mutants, with an approximately threefold decrease in ATP levels.

Pgknubian mutants show a dramatic reduction in lifespan, with a decrease in the T50 (age at which 50% of the culture has died) by 75%, indicating a highly significant negative effect of reduced resting ATP levels on lifespan. In addition to reduced lifespan, Pgknubian animals are more sluggish than control animals at room temperature, even shortly after pupation before any change in viability is noted. Behavioural assays performed on 4- to 5-day old Pgknubian adults reveals a decrease in both climbing ability and spontaneous locomotion, consistent with a general reduction in locomotor activity secondary to altered ATP generation.

Pgknubian mutant larvae exhibit a >50% decrease in distance travelled and locomotor speed compared to wild-type larvae. These differences in motor output are accounted for by a decrease in the time spent in locomotion and a dramatic reduction in locomotor cycle frequency. In general, Pgknubian animals spend approximately 20% less time in locomotion, with a much higher propensity for pauses with head swinging/turning behavior, as manifested by an increase in direction changes in Pgknubian larvae.

Similar to controls, Pgknubian mutant larvae display approximately 54.6 varicosities per muscle fiber.

In general, average bouton diameter is larger at Pgknubian synapses compared to controls, especially in type 1B boutons and in branching boutons with two or more branch points.

Evoked synaptic transmission is not altered in Pgknubian mutants at 22oC. The amplitudes of evoked excitatory junctional potentials (EJPs) and resting membrane potential are similar to controls. In addition, there is no change in paired pulse facilitation in Pgknubian mutants, indicating that short-term plasticity is intact. A slight reduction in spontaneous miniature EJP frequency from 1.4Hz in control animals to 1.1Hz in Pgknubian is observed, suggesting a smaller recycling pool of synaptic vesicles in the mutant. Motor pattern bursts are reduced by one-half in Pgknubian mutants, with only a mild reduction in burst duration compared to wild-type. Upon shifting to 36oC, control animals show a two-fold increase in the frequency of motor pattern bursts. In contrast, the output of the central pattern generator is abolished completely in Pgknubian mutants at the elevated temperatures.

The resting membrane potential is lower in Pgknubian mutants than in controls at 36oC, indicating that there is an immediate effect on membrane excitability that causes muscle membrane depolarisation compared with controls. Pgknubian mutants display a stimulation-dependent reduction in evoked EJPs compared with controls. During 10Hz nerve stimulation Pgknubian larvae show a gradual reduction in EJP amplitude, with a complete loss of synaptic transmission by 3 minutes on average. In contrast, without 10Hz nerve stimulation the amplitude of evoked responses in Pgknubian animals show little change. After the onset of 10Hz stimulation, however, Pgknubian synapses undergo a rapid reduction in response similar to animals that are stimulated shortly after the temperature is shifted to 36oC.

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Mutant
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Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Pgknubian
Name Synonyms
Secondary FlyBase IDs
    References (1)