FB2024_03 , released June 25, 2024
Allele: Hsap\TARDBPG298S.UAS.YFP
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General Information
Symbol
Hsap\TARDBPG298S.UAS.YFP
Species
H. sapiens
Name
FlyBase ID
FBal0296676
Feature type
allele
Associated gene
Hsap\TARDBP
Associated Insertion(s)
Carried in Construct
P{UAS-TARDBP.G298S.YFP}
Also Known As
TDP-43G298S, TDPG298S
Key Links
Transgenic product class
missense_variant
(Estes et al., 2013)
Mutagen
Nature of the Allele
Transgenic product class
missense_variant
(Estes et al., 2013)
Mutagen
in vitro construct
(Estes et al., 2013)
Progenitor genotype
Carried in construct
P{UAS-TARDBP.G298S.YFP}
Cytology
Description

UASt regulatory sequences drive expression of a G298S mutant of Hsap\TARDBP with a C-terminal YFP tag.

(Estes et al., 2013)
Allele components
Component
Use(s)
Regulatory region(s)
UASt
Encoded product / tool
Hsap\TARDBP
Tagged with
YFP
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 Fmr1UAS.YFP
      (Coyne et al., 2015)
      is exacerbated by Fmr1GD1288
      (Coyne et al., 2015)
      is exacerbated by Fmr1Δ50M
      (Coyne et al., 2015)
      is exacerbated by Pabp255
      (Chou et al., 2015)
      is ameliorated by futschEP1419
      (Coyne et al., 2014)
      model of  amyotrophic lateral sclerosis type 10
      is ameliorated by Hsap\IDH3AUAS.cUa
      (Loganathan et al., 2022)
      is ameliorated by Idh3aUAS.cUa
      (Loganathan et al., 2022)
      is exacerbated by PfkHMS01324
      (Manzo et al., 2019)
      is ameliorated by PfkUAS.cTa
      (Manzo 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.
      (Estes et al., 2013)
      TARDBP:p.Gly298Ser
      (FlyBase curators, 2019-)
      Variants Synonym(s)
      Associated human disease model(s)
      External database links
      ClinVar: TARDBP_5232
      Comments concerning this variant
      Phenotypic Data
      Phenotypic Class
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      Overexpression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP driven in motor neurons by Scer\GAL4Toll-6-D42 in larvae results in locomotor dysfunction (significant increase in the amount of time taken for the larva to turn from dorsal side and resume crawling on the ventral side).

      (Chou et al., 2015)

      Ectopic expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the control of Scer\GAL4GMR.PU results in an age-dependent depigmentation phenotype in the adult eye indicative of neurodegeneration.

      Ectopic expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the Scer\GAL4Toll-6-D42 driver significantly lengthens the time it takes for larvae to roll over in a turning assay and reduces adult life span compared to wild-type.

      Ectopic expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the control of Scer\GAL4Toll-6-D42 results in significantly increased number of satellite boutons and significantly decreased density of futsch positive loops on synaptic boutons on neuromuscular junctions of third instar larvae compared to wild-type controls.

      (Coyne et al., 2015)

      Expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP in motor neurons under the control of Scer\GAL4D42 is lethal at the pupal or pharate adult stage. Few pharate adults eclose but cannot extend their wings. Larvae expressing Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa display locomotor dysfunction in turning assays. Treatment with pioglitazone results in improved larval locomotor function and the survival of the animals to adulthood. However, pioglitazone-treatment is not effective at improving the lifespan of the transgenic adults.

      Expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP in glia under the control of Scer\GAL4repo causes locomotor function abnormalities. Pioglitazone-treatment mitigates the locomotor dysfunction phenotype. However, pioglitazone-treatment is not effective at improving the lifespan of the transgenic adults expressing Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP in glia.

      Muscle-specific expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP using Scer\GAL4BG487 results in larval locomotor defects which is not mitigated by pioglitazone-treatment.

      (Joardar et al., 2015)

      This expression results in a decreased adult lifespan compared to controls.

      (Coyne et al., 2014)

      Expression of Scer\GAL4GMR.PU>Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP leads to age- and dose-dependent neurodegeneration as indicated by depigmentation in the eye.

      Expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP in motor neurons under the control of Scer\GAL4D42 results in nuclear morphology defects and smaller synapses compared with wild-type. This anatomical phenotype is accompanied by an impairment in locomotor function, as indicated by a significant increase in larval turning time compared with controls.

      Compared with controls, expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP in glial cells under the control of Scer\GAL4repo.PU results in significantly smaller neuromuscular junctions (NMJs) with a decreased number of synaptic boutons. When tested for their ability to turn, larvae expressing the transgene in glia also exhibit a significant impairment in locomotor function.

      Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP-expression leads to a mismatch of pre- and post-synaptic areas. Expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP in motor neurons leads to a significant increase in the area of pre-synaptic active zones, while its expression in glia results in reduction in the size of post-synaptic areas.

      Both motor neuron and glial expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP can lead to alterations in adult locomotion and sleep patterns.

      (Estes et al., 2013)
      External Data
      Interactions
      Show genetic interaction network for Enhancers & Suppressors
      Phenotypic Class
      Enhanced by
      Suppressed by
      NOT suppressed by
      Other
      Phenotype Manifest In
      Additional Comments
      Genetic Interactions
      Statement
      Reference
      Xenogenetic Interactions
      Statement
      Reference

      Pabp255 significantly enhances locomotor dysfunction seen in larvae with expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP driven by Scer\GAL4GMR.PU.

      (Chou et al., 2015)

      The depigmentation phenotype in the adult eye and the lengthened time it takes for larvae to roll over in a turning assay characteristic for animals expressing Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the control of Scer\GAL4GMR.PU or Scer\GAL4Toll-6-D42 respectively, are exacerbated further by co-expression of Fmr1GD1288 RNAi. However, co-expression of Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP and Fmr1GD1288 under the Scer\GAL4Toll-6-D42 driver is pupal stage lethal.

      The depigmentation phenotype in the adult eye and the lengthened time it takes for larvae to roll over in a turning assay characteristic for animals expressing Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the control of Scer\GAL4GMR.PU or Scer\GAL4Toll-6-D42 respectively, are restored by co-expression of Fmr1Scer\UAS.T:Avic\GFP-YFP.

      The short adult life span, the increased number of satellite boutons along with the reduction in the density of futsch positive loops on synaptic boutons on neuromuscular junctions of third instar larvae characteristic for animals expressing Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the control of Scer\GAL4Toll-6-D42 can be fully (satellite boutons) or partially (loops density on synaptic boutons, adult life span) rescued by co-expression of Fmr1Scer\UAS.T:Avic\GFP-YFP.

      The depigmentation phenotype in the adult eye and the lengthened time it takes for larvae to roll over in a turning assay characteristic for animals expressing Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP under the control of Scer\GAL4GMR.PU or Scer\GAL4Toll-6-D42 respectively, are exacerbated further by combination with Fmr1Δ50M in heterozygous state.

      (Coyne et al., 2015)

      Pioglitazone can no longer rescue the Scer\GAL4D42>Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP-dependent larval turning defects in a heterozygous Eip75BΔ51 genetic background.

      Pioglitazone can no longer rescue the Scer\GAL4D42>Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP-dependent larval turning defects when Eip78CJF02258 is co-expressed.

      (Joardar et al., 2015)

      Expression of futschHMS02000 does not suppress the larval turning phenotype seen when Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP is expressed under the control of Scer\GAL4D42, but the flies are lethal at the pupal stage.

      Expression of futschEP1419 partially suppresses the larval turning and reduced lifespan phenotypes seen when Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP is expressed under the control of Scer\GAL4D42.

      Expression of futschEP1419 fully suppresses the reduction in boutons compared with controls seen when Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP is expressed under the control of Scer\GAL4D42. The increase in satellite bouton number in the larval NMJ is suppressed to control levels.

      (Coyne et al., 2014)
      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 (5)
      Reported As
      Symbol Synonym
      Hsap\TARDBPG298S.Scer\UAS.T:Avic\GFP-YFP
      Hsap\TARDBPG298S.UAS.YFP
      TDP-43G298S
      (Loganathan et al., 2022, Manzo et al., 2019)
      TDPG298S
      (Joardar et al., 2015)
      hG298S
      (Chou et al., 2015)
      Name Synonyms
      Secondary FlyBase IDs
        References (10)