FlyBase Allele Report: Dmel\spas[K467R.UAS]

General Information

Symbol

Dmel\spas^K467R.UAS

Species

D. melanogaster

Name

FlyBase ID

FBal0295067

Feature type

allele

Associated gene

Dmel\spas

Associated Insertion(s)

Carried in Construct

P{UAS-spas.K467R}

Also Known As

UAS-Dspastin-K467R

Key Links

Genomic Maps

JBrowse

Transgenic product class

missense_variant

(Orso et al., 2005)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Orso et al., 2005)

Mutagen

in vitro construct

(Orso et al., 2005)

Progenitor genotype

Carried in construct

P{UAS-spas.K467R}

Cytology

Description

UAS regulatory sequences drive expression of spas containing the amino acid replacement K467R (this mutation corresponds to the pathogenic K388R mutation in the human ortholog).

(Orso et al., 2005)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

spas

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

3R:24,040,933..24,040,933 [+]

Nucleotide change:

A24040933G

Amino acid change:

Reported amino acid change:

K467R

Comment:

K467R mutation is relative to isoform spas-PC and spas-PD; analogous mutation in human SPAST implicated in spastic paraplegia 4; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator.

(Orso et al., 2005)

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 hereditary spastic paraplegia

CEA

(Orso et al., 2005)

model of hereditary spastic paraplegia 4

CEA

(Vajente et al., 2019)

Modifiers Based on Experimental Evidence ( 0 )

Disease

Interaction

References

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

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Orso et al., 2005)

SPAST:p.Lys388Arg

(FlyBase curators, 2019-)

Variants Synonym(s)

SPAST:p.Lys356Arg

Associated human disease model(s)

spastic paraplegia 4

External database links

ClinVar: 1442734

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal neuroanatomy | adult stage, with Scer\GAL4^elav.PU

(Orso et al., 2005)

abnormal neuroanatomy | adult stage, with Scer\GAL4^elav.PU, spas^5.75

(Orso et al., 2005)

abnormal neuroanatomy | third instar larval stage, with Scer\GAL4^elav.PU

(Orso et al., 2005)

partially lethal - majority die, with Scer\GAL4^Tub.PU

(Orso et al., 2005)

short lived, with Scer\GAL4^elav.PU

(Orso et al., 2005)

Phenotype Manifest In

adult brain, with Scer\GAL4^elav.PU

(Orso et al., 2005)

adult brain, with Scer\GAL4^elav.PU, spas^5.75

(Orso et al., 2005)

embryonic/larval neuromuscular junction | third instar larval stage, with Scer\GAL4^elav.PU

(Orso et al., 2005)

Detailed Description

Statement

Reference

No eye phenotypes are seen when spas^{dsRNA.Scer\UAS} is expressed under the control of Scer\GAL4^GMR.PU.

The partial lethality seen when spas^{K467R.Scer\UAS} is expressed under the control of Scer\GAL4^tub.PU is partially rescued upon administration of the microtubule destabilizing drug vinblastine, but not nocodazole.

Expression of spas^{K467R.Scer\UAS} under the control of Scer\GAL4^elav.PU results in a decrease in larval synaptic area and arborization, as well as the accumulation of hyperstable microtubules at the NMJ presynaptic terminal. Lifespan is reduced compared to controls and the flies show a progressive design in climbing ability. The climbing and lifespan defects are partially rescued upon administration of the microtubule destabilizing drug vinblastine, but not nocodazole. The synapse and microtubule phenotypes are also suppressed by vinblastine. Modest neurodegeneration is seen in the adult brain.

One copy of spas^5.75 enhances the neurodegeneration seen in the adult brain when spas^{K467R.Scer\UAS} is expressed under the control of Scer\GAL4^elav.PU. Significant degeneration is seen, particularly in the medulla.

(Orso et al., 2005)

External Data

Linkouts

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

Rescues

spas^K467R.UAS/Scer\GAL4^GMR.PU rescues spas^UAS.cTa

(Orso et al., 2005)

Comments

Expression of spas^{K467R.Scer\UAS} suppresses the rough eye phenotype seen when spas^Scer\UAS.cTa is expressed under the control of Scer\GAL4^GMR.PU.

(Orso et al., 2005)

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

spas^{K467R.Scer\UAS}

spas^K467R.UAS

Name Synonyms

Secondary FlyBase IDs

References (4)

Report Sections

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