FlyBase Allele Report: Hsap\FUS[P525L.10x.UAS.Tag:FLAG]

General Information

Symbol

Hsap\FUS^{P525L.10x.UAS.Tag:FLAG}

Species

H. sapiens

Name

FlyBase ID

FBal0265764

Feature type

allele

Associated gene

Hsap\FUS

Associated Insertion(s)

Carried in Construct

P{10xUAS-FUS.P525L}

Also Known As

UAS-FL-FUS^P525L

Key Links

Transgenic product class

missense_variant

(Wang et al., 2011)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Wang et al., 2011)

Mutagen

in vitro construct

(Wang et al., 2011)

Progenitor genotype

Carried in construct

P{10xUAS-FUS.P525L}

Cytology

Description

Ten copies of UAS regulatory sequences drive expression of a P525L mutant Hsap\FUS cDNA fused to an N-terminal Tag:FLAG epitope tag.

(Wang et al., 2011)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

Hsap\FUS

Tagged with

Tag:FLAG

epitope tag

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

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 amyotrophic lateral sclerosis

CEA

(Joardar et al., 2015)

model of amyotrophic lateral sclerosis type 6

CEC

(Cacciottolo et al., 2019)

CEA

(Farrugia et al., 2022)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

ameliorates amyotrophic lateral sclerosis

modeled by caz³⁸³

(Baldwin et al., 2016)

model of amyotrophic lateral sclerosis type 6

is exacerbated by Gem3^ΔN.UAS

(Cacciottolo et al., 2019)

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

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Wang et al., 2011)

FUS:p.Pro525Leu

(FlyBase curators, 2019-)

Variants Synonym(s)

FUS:p.Pro521Leu

FUS:p.Pro524Leu

Associated human disease model(s)

amyotrophic lateral sclerosis 6 with or without frontotemporal dementia

External database links

ClinVar: FUS_280110

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

embryonic/larval motor neuron | third instar larval stage, with Scer\GAL4^CCAP.PU

(Baldwin et al., 2016)

embryonic/larval neuromuscular junction | third instar larval stage, with Scer\GAL4^VGlut1-OK371

(Machamer et al., 2014)

presynaptic active zone | third instar larval stage, with Scer\GAL4^VGlut1-OK371

(Machamer et al., 2014)

synapse, with Scer\GAL4^VGlut1-OK371

(Machamer et al., 2014)

Detailed Description

Statement

Reference

The expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} under the control of Scer\GAL4^Toll-6-D42 does not lead to any obvious defects in viability or third instar larval locomotion, but induces a significant and progressive decrease in adult locomotion, as compared to controls.

The expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} under the control of Scer\GAL4^CCAP.PI leads to a decrease in axonal transport of NPY-positive vesicles (i.e. a significant decrease in anterograde transport and a significant increase in the stationary fraction), but not of mitochondria, in third instar larval motor neurons, as compared to controls.

(Baldwin et al., 2016)

Expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} in motor neurons under the control of Scer\GAL4^D42 results in impaired larval locomotion, which is rescued by pioglitazone-treatment. However, pioglitazone-treatment is not effective in improving lifespan in adult transgenic animals.

(Joardar et al., 2015)

Scer\GAL4^VGlut-OK371>Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG}-expressing animals display a reduction in the number of presynaptic active zones compared with wild-type.

Compared with wild-type, third instar larvae expressing Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} under the control of Scer\GAL4^VGlut-OK371 display an approximately 25% reduction in evoked excitatory junction potential (EJP) amplitude. The reduction of quantal content in these animals reaches statistical significance.

Analysis of synaptic fatigue reveals that animals expressing Scer\GAL4^VGlut-OK371>Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} fatigue faster than control animals.

(Machamer et al., 2014)

Overexpression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} in motor neurons via Scer\GAL4^RapGAP1-OK6 does not result in neuromuscular junction (NMJ) expansion.

Overexpression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} in neurons has no significant effect on locomotion.

Overexpression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} has no effect on longevity.

(Wang et al., 2011)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Suppressor of

Statement

Reference

Hsap\FUS^{P525L.10x.UAS.Tag:FLAG}/Scer\GAL4^Toll-6-D42 is a suppressor | partially of partially lethal - majority die phenotype of caz³⁸³

(Baldwin et al., 2016)

Scer\GAL4^elav-C155/Hsap\FUS^{P525L.10x.UAS.Tag:FLAG} is a suppressor of partially lethal - majority die phenotype of CG32576^+t5.0, caz³⁸³

(Wang et al., 2011)

Scer\GAL4^elav-C155/Hsap\FUS^{P525L.10x.UAS.Tag:FLAG} is a suppressor | partially of abnormal locomotor behavior phenotype of CG32576^+t5.0, caz³⁸³

(Wang et al., 2011)

Scer\GAL4^elav-C155/Hsap\FUS^{P525L.10x.UAS.Tag:FLAG} is a suppressor | partially of short lived phenotype of CG32576^+t5.0, caz³⁸³

(Wang et al., 2011)

Phenotype Manifest In

Suppressor of

Statement

Reference

Scer\GAL4^CCAP.PU/Hsap\FUS^{P525L.10x.UAS.Tag:FLAG} is a suppressor | partially of embryonic/larval motor neuron | third instar larval stage phenotype of caz³⁸³

(Baldwin et al., 2016)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

The expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} under the control of Scer\GAL4^Toll-6-D42 nearly fully suppresses the semi-lethality, the decreased third instar larval crawling capacity and the decreased adult locomotor capacity observed in caz³⁸³ homozygotes.

The expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} under the control of Scer\GAL4^CCAP.PI fully suppresses the decreased axonal transport of mitochondria, but not of (NPY-positive) vesicles, observed in caz³⁸³ homozygous third instar larval motor neurons.

(Baldwin et al., 2016)

Expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} in the nervous system under the control of Scer\GAL4^elav-C155 almost completely rescues the adult viability of males hemizygous for the 'caz¹' mutant chromosome (Df(1)383 onto which a transgene containing CG32576^+t5.0 has been recombined to provide CG32576[+] function) - the level of rescue seen with Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} is not significantly different from that seen when a transgene containing wild-type caz is expressed using the same driver.

Expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} under the control of Scer\GAL4^elav-C155 partially rescues the locomotor defects seen in caz¹/Y adult males.

Expression of Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG} under the control of Scer\GAL4^elav-C155 does not rescue the the median lifespan of adult caz¹/Y escapers, although maximum lifespan is increased.

(Wang et al., 2011)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (3)

Reported As

Symbol Synonym

FUS^P525L

(Baldwin et al., 2016)

Hsap\FUS^{P525L.10x.Scer\UAS.T:Zzzz\FLAG}

Hsap\FUS^{P525L.10x.UAS.Tag:FLAG}

Name Synonyms

Secondary FlyBase IDs

References (8)

Report Sections

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