FB2025_01 , released February 20, 2025
Allele: Hsap\FUSP525L.UAS.RFP(Unk),Tag:HA
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General Information
Symbol
Hsap\FUSP525L.UAS.RFP(Unk),Tag:HA
Species
H. sapiens
Name
FlyBase ID
FBal0285344
Feature type
allele
Associated gene
Hsap\FUS
Associated Insertion(s)
Carried in Construct
P{UAS-hFUS-RFP.P525L}
Also Known As
UAS-P525L-FUS-RFP, FUS P525L-RFP
Key Links
Transgenic product class
missense_variant
(Chen et al., 2011)
Mutagen
Nature of the Allele
Transgenic product class
missense_variant
(Chen et al., 2011)
Mutagen
in vitro construct
(Chen et al., 2011)
Progenitor genotype
Carried in construct
P{UAS-hFUS-RFP.P525L}
Cytology
Description

UASt regulatory sequences drive expression of mutated Hsap\FUS coding sequences (carries the amino acid replacement P525L) fused at the C-terminal with an unspecified red fluorescent protein and a Tag:HA epitope.

(Chen et al., 2011)
Allele components
Component
Use(s)
Regulatory region(s)
UASt
Encoded product / tool
Hsap\FUS
Tagged with
RFP(Unk)
Tag:HA
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 )
      Modifiers Based on Experimental Evidence ( 1 )
      Disease
      Interaction
      References
      model of  amyotrophic lateral sclerosis
      is ameliorated by Hsp60BVDRC.cUa
      (Deng et al., 2015)
      model of  amyotrophic lateral sclerosis type 6
      is exacerbated by Pink1UAS.cYa
      (Chen et al., 2016)
      is exacerbated by Gem3ΔN.UAS
      (Cacciottolo et al., 2019)
      is ameliorated by ATPsynβJF02892
      (Deng et al., 2018)
      is ameliorated by ClpPKK100861
      (Deng et al., 2018)
      is ameliorated by LonHMS01940
      (Deng et al., 2018)
      is ameliorated by Trap1KK102212
      (Deng et al., 2018)
      Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
       
      Disease-implicated variant(s)
       
      This allele represents a human variant implicated in disease.
      (Chen et al., 2011)
      FUS:p.Pro525Leu
      (FlyBase curators, 2019-)
      Variants Synonym(s)
      FUS:p.Pro521Leu
      FUS:p.Pro524Leu
      Associated human disease model(s)
      External database links
      ClinVar: FUS_280110
      Comments concerning this variant
      Phenotypic Data
      Phenotypic Class
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      Expression of Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 under the control of Scer\GAL4Toll-6-D42 results in decreased size of axonal mitochondria in motor neurons in the A3 abdominal segment of third instar larvae. Expression under the Scer\GAL4GMR.PU driver leads to rough eye phenotype due to ommatidial fusion and interommatidial bristles disorganization as well as loss of pigmentation in adult flies.

      (Deng et al., 2015)

      Flies expressing Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 in the developing eye, under the control of Scer\GAL4GMR.PF, exhibit severe eye abnormalities. They show a reduction in red eye pigment as compared to controls, beginning at eclosion. No necrosis-like darkened area are observed, although rough eye surfaces with disrupted ommatidia and bristle organisation are seen. SEM at higher magnification reveals ommatidial loss, ommatidial fusion, bristle loss or ectopic bristles and aberrant bristle budding in the inter-ommatidial spaces.

      The surface of the eye appears relatively normal in 5-day-old flies expressing Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 under the control of Scer\GAL4GMR.PF. However, by day 15 this surface has rapidly deteriorated.

      1-day-old flies expressing Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 under the control of Scer\GAL4ey-OK107 exhibit a decrease in the size of the mushroom bodies and thinner lobes as compared to control flies. Axonal loss and lobe involvement is not symmetric, but often in the a 'group' fashion. Once a particular lobe is affected, it progressively degenerates. In many cases, one of the mushroom bodies may exhibit more degeneration than the mushroom body on the other side.

      Expression of Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 in the glutamatergic neurons of the ventral nerve cord, under the control of Scer\GAL4ey-OK107 leads to disruption in motor neuron clusters, with cell body swelling in a fraction of motor neurons, especially in the posterior segment.

      A significant decrease in neuromuscular junction bouton number is observed in flies expressing Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 in glutamatergic neurons of the ventral nerve cord, under the control of Scer\GAL4VGlut-OK371, as compared to controls. Bouton size in these flies is significantly reduced as compared to controls.

      Larval locomotion is significantly reduced in flies expressing Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 under the control of Scer\GAL4VGlut-OK371. These larvae move more slowly with their tails lifted rather than anchored on the supporting surface, possibly as a result of paralysis of the posterior segments. These locomotion defects can be so severe that the flies cannot climb up the wall and/or hardly move. Most Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1-expressing pupae fail to hatch.

      (Chen et al., 2011)
      External Data
      Interactions
      Show genetic interaction network for Enhancers & Suppressors
      Phenotypic Class
      NOT Enhanced by
      Suppressed by
      NOT suppressed by
      Phenotype Manifest In
      NOT Enhanced by
      Suppressed by
      NOT suppressed by
      Additional Comments
      Genetic Interactions
      Statement
      Reference
      Xenogenetic Interactions
      Statement
      Reference

      The adult eye phenotype (rough surface due to ommatidial fusion and disorganization of interommatidial bristle pattern, pigmentation loss) characteristic for flies expressing Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 under the control of Scer\GAL4GMR.PU is partially rescued by co-expression of Hsp60BVDRC.cUa and to a lesser extent also by Hsp60AVDRC.cUa or Hsp60CVDRC.cUa but neither the rough eye phenotype nor the pigmentation loss is significantly affected by co-expression of any of the following: Hsp60DGD8786, Drp1Scer\UAS.cUa, Drp1dsRNA.Scer\UAS.cUa or Drp1K38A.Scer\UAS.T:Ivir\HA1. The decreased size of axonal mitochondria in motor neurons as well as the locomotor defects (tail paralysis) observed in third instar larvae expressing Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 under the control of Scer\GAL4Toll-6-D42 or Scer\GAL4VGlut-OK371, respectively, is also significantly improved by co-expression of Hsp60BVDRC.cUa.

      (Deng et al., 2015)
      Complementation and Rescue Data
      Comments
      Images (0)
      Mutant
      Wild-type
      Stocks (0)
      Notes on Origin
      Discoverer
      Comments
      Comments

      In respect to eye and motor neuron degeneration, the following transgenes form an allelic series when expressed by Scer\GAL4GMR.PF or Scer\GAL4ey-OK107, from mildest to most severe: Hsap\FUSWT.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 < Hsap\FUSR524S.Scer\UAS.T:Disc\RFP,T:Ivir\HA1 < Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1.

      (Chen et al., 2011)
      External Crossreferences and Linkouts ( 0 )
      Synonyms and Secondary IDs (2)
      Reported As
      Symbol Synonym
      Hsap\FUSP525L.Scer\UAS.T:Disc\RFP,T:Ivir\HA1
      Hsap\FUSP525L.UAS.RFP(Unk),Tag:HA
      Name Synonyms
      Secondary FlyBase IDs
        References (10)