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General Information
Symbol
Dmel\KhcN262S.UAS
Species
D. melanogaster
Name
FlyBase ID
FBal0281726
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
point mutation
Nucleotide change:

A16269478G

Reported nucleotide change:

A?G

Amino acid change:

N262S | Khc-PA

Reported amino acid change:

N262S

Comment:

Analogous mutation in human KIF5A implicated in spastic paraplegia 10; mutation carried on in vitro construct.

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

UAS regulatory sequences drive expression of the Khc SD02406 cDNA, which has been mutated to contain the amino acid replacement N262S (equivalent to the N256S mutation in the KIF5A gene which results in hereditary spastic paraplegia in humans).

Allele components
Product class / Tool use(s)
Encoded product / tool
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
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

Larvae expressing KhcN262S.Scer\UAS under the control of Scer\GAL4D42 at either 25 or 29[o]C initially display a "tail-flipping" phenotype, and the paralysis then ascends from posterior to anterior until the larvae can only move their head. Complete paralysis then ensues, with lethality in the second or third instar. Larval growth is delayed compared to wild type. Before paralysis, larval locomotion speed is reduced compared to wild type. Axonal swellings are seen in the mutant larvae. These swellings are filled with mitochondria, pre-lysosomal vacuoles, autophagosomes and multivesicular bodies.

A strong reduction in both anterograde and retrograde flux of mitochondria along the axons is seen in larvae expressing KhcN262S.Scer\UAS under the control of Scer\GAL4D42.

Larvae expressing KhcN262S.Scer\UAS under the control of Scer\GAL4D42 show a strong reduction in the number and density of mitochondria at neuromuscular junctions (NMJs) 6/7 in segment A2, while there is no obvious reduction in mitochondrial abundance in motorneuron cell bodies. The area of NMJ 6/7 is strongly reduced compared to controls in segment A5 but not in segment A2. The number of synapses at the NMJ in segment A2 is not significantly different from wild type, while the number of synapses at the NMJ in segment A5 is significantly reduced. A significant degree of neurodegenerative alterations are seen at NMJ 6/7 of segment A5 in mutant larvae.

No evidence for increased apoptosis of motorneurons is seen in mid-third instar larvae expressing KhcN262S.Scer\UAS under the control of Scer\GAL4D42.

The evoked excitatory junctional potential (EJP) of the NMJ is drastically reduced in amplitude in larvae expressing KhcN262S.Scer\UAS under the control of Scer\GAL4D42, while the half-width time is increased. The amplitude of the miniature EJP is slightly, but not significantly, increased in the mutant larvae. Quantal content is significantly reduced.

Adults with a 25% reduction in lifespan are recovered when KhcN262S.Scer\UAS is expressed under the control of Scer\GAL4D42 at 18[o]C. These animals cannot sustain stable flight if forced to fly, but fall to the ground. At rest they have a held-up wing phenotype. No evidence of degeneration of the indirect flight muscles can be seen.

16 day old adults in which KhcN262S.Scer\UAS is expressed under the control of Scer\GAL4elav.PU after eclosion (the temperature sensitive Scer\GAL80ts.αTub84B allele is used to limit expression prior to eclosion) are essentially unable to climb.

A strong reduction in both anterograde and retrograde flux of mitochondria along the axons is seen in larvae co-expressing both KhcScer\UAS.cFa and KhcN262S.Scer\UAS under the control of Scer\GAL4D42.

Quantal content at the neuromuscular junction is significantly reduced in larvae co-expressing both KhcScer\UAS.cFa and KhcN262S.Scer\UAS under the control of Scer\GAL4D42.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Partially rescued by
Comments

Co-expression of KhcScer\UAS.cFa ameliorates the paralysis phenotype seen in larvae expressing KhcN262S.Scer\UAS under the control of Scer\GAL4D42 at either 25 or 29[o]C , with the larvae displaying a tail-flipping phenotype at a stage where larvae expressing only KhcN262S.Scer\UAS under the control of Scer\GAL4D42 can only move their heads.

Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
KhcN262S.Scer\UAS
KhcN262S.UAS
Name Synonyms
Secondary FlyBase IDs
    References (1)