FB2024_03 , released June 25, 2024
Allele: Hsap\TARDBPUAS.YFP.cEa
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General Information
Symbol
Hsap\TARDBPUAS.YFP.cEa
Species
H. sapiens
Name
Saccharomyces cerevisiae UAS construct a of Estes
FlyBase ID
FBal0277060
Feature type
allele
Associated gene
Hsap\TARDBP
Associated Insertion(s)
Carried in Construct
P{UAS-TARDBP.YFP.E}
Also Known As
TDPWT, hwt, TDP-43WT
Key Links
Transgenic product class
wild_type
(Estes et al., 2011)
Mutagen
Nature of the Allele
Transgenic product class
wild_type
(Estes et al., 2011)
Mutagen
in vitro construct
(Estes et al., 2011)
Progenitor genotype
Carried in construct
P{UAS-TARDBP.YFP.E}
Cytology
Description

UAS regulatory sequences drive expression of wild type Hsap\TARDBP tagged at the C-terminal end with YFP.

(Estes et al., 2011)
Allele components
Component
Use(s)
Regulatory region(s)
UAS
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 ameliorated by BacA\p35UAS.cHa
      (Estes et al., 2011)
      is ameliorated by Hsap\HSPA1LUAS.cWa
      (Estes et al., 2011)
      is exacerbated by Prosβ21.UAS
      (Estes et al., 2011)
      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 dlpUAS.cBa
      (Godfrey et al., 2023)
      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)
       
      Phenotypic Data
      Phenotypic Class

      abnormal eye color | adult stage, with Scer\GAL4GMR.PU

      (Coyne et al., 2015)

      abnormal locomotor behavior | adult stage, with Scer\GAL4Toll-6-D42

      (Estes et al., 2011)

      abnormal locomotor behavior | larval stage, with Scer\GAL4Toll-6-D42

      (Chou et al., 2015, Coyne et al., 2014)

      abnormal locomotor behavior | third instar larval stage, with Scer\GAL4BG487

      (Joardar et al., 2015)

      abnormal locomotor behavior | third instar larval stage, with Scer\GAL4repo

      (Joardar et al., 2015)

      abnormal locomotor behavior | third instar larval stage, with Scer\GAL4Toll-6-D42

      (Coyne et al., 2015, Joardar et al., 2015, Estes et al., 2011)

      abnormal neuroanatomy, with Scer\GAL4Toll-6-D42

      (Coyne et al., 2014)

      abnormal neuroanatomy | adult stage, with Scer\GAL4GMR.PF

      (Estes et al., 2011)

      abnormal neuroanatomy | adult stage, with Scer\GAL4GMR.PU

      (Chou et al., 2015)

      abnormal neuroanatomy | larval stage, with Scer\GAL4Toll-6-D42

      (Estes et al., 2011)

      abnormal neuroanatomy | third instar larval stage, with Scer\GAL4Toll-6-D42

      (Coyne et al., 2015)

      decreased cell number | adult stage, with Scer\GAL4GMR.PF

      (Estes et al., 2011)

      decreased cell number | adult stage, with Scer\GAL4Toll-6-D42

      (Estes et al., 2011)

      partially lethal - majority die, with Scer\GAL4Toll-6-D42

      (Joardar et al., 2015)

      partially lethal - majority die | larval stage | heat sensitive, with Scer\GAL4Toll-6-D42

      (Estes et al., 2011)

      partially lethal - majority die | pupal stage | heat sensitive, with Scer\GAL4Toll-6-D42

      (Estes et al., 2011)

      short lived, with Scer\GAL4Toll-6-D42

      (Coyne et al., 2015, Joardar et al., 2015, Coyne et al., 2014, Estes et al., 2011)

      some die during immature adult stage | recessive, with Scer\GAL4Toll-6-D42

      (Joardar et al., 2015)

      some die during P-stage, with Scer\GAL4Toll-6-D42

      (Joardar et al., 2015)

      visible, with Scer\GAL4GMR.PU

      (Chou et al., 2015)

      visible | adult stage, with Scer\GAL4GMR.PF

      (Estes et al., 2011)
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      Overexpression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa driven in the adult retina by Scer\GAL4GMR.PU causes a neurodegeneration phenotype, with visible depigmentation.

      Overexpression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa in glia.

      Muscle-specific expression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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 Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa in the eye under the control of Scer\GAL4GMR.PF has no visible phenotype in the eye at 25[o]C in 0-3 day old flies but visible loss of pigmentation is seen at 5 days old and worsens with age. Cell loss and neurodegeneration is seen in retinal sections. When the temperature is increased to 29[o]C visible retinal neurodegeneration can be seen in 1-2 day old flies.

      Expression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa under the control of Scer\GAL4D42 results in a decreased number of boutons in the larval neuromuscular junction. The number of synaptic vesicles is also reduced compared to wild type, and supernumerary satellite boutons are present. The number of axonal branches is reduced.

      Expression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa under the control of Scer\GAL4D42 results in locomotor defects in third instar larvae. Crawling larvae rolled ventral side up take longer to turn back to dorsal side up.

      78% of flies expressing Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa under the control of Scer\GAL4D42 fail to live to 30 days at 18[o]C, compared to only 30% of controls. Very few flies survive to adulthood at 25[o]C.

      Flies expressing Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa under the control of Scer\GAL4D42 exhibit a progressive decline in their ability to climb at 18[o]C. At 2 days old 76.3% of flies are able to climb compared to 94.3% of controls. By 30 days old only 3.1% of flies are able to climb compared to 25% of controls.

      Expression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa under the control of Scer\GAL4D42 does not result in motor neuron apoptosis in the larval ventral ganglia.

      Expression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa under the control of Scer\GAL4D42 results in a dramatic loss of motor neurons in the adult thoracic ganglia.

      (Estes et al., 2011)
      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 enhances the neurodegeneration phenotype (visible as depigmentation of the eye) in flies with expression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa driven by Scer\GAL4GMR.PU.

      Pabp255 significantly enhances locomotor dysfunction seen in larvae with expression of Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa-dependent larval turning defects in a heterozygous Eip75BΔ51 genetic background.

      Pioglitazone can no longer rescue the Scer\GAL4D42>Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa-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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa is expressed under the control of Scer\GAL4D42.

      Expression of futschEP1419 fully suppresses the reduction in boutons compared with controls seen when Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa 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)

      Expression of TBPHGD6943 enhances the third instar larval locomotor defects seen when Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa is expressed in motor neurons under the control of Scer\GAL4D42.

      Expression of Hsap\HSPA1LScer\UAS.cWa partially suppresses the eye pigmentation phenotype seen in 15 day old adults when Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa is expressed under the control of Scer\GAL4D42 at 25[o]C.

      Expression of BacA\p35Scer\UAS.cHa partially suppresses the eye pigmentation phenotype seen in 15 day old adults when Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa is expressed under the control of Scer\GAL4D42 at 25[o]C.

      Expression of Prosβ21.Scer\UAS enhances the eye pigmentation phenotype seen when Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa is expressed under the control of Scer\GAL4GMR.PF. This enhancement is seen throughout adult life at 25[o]C.

      (Estes 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 (7)
      Reported As
      Symbol Synonym
      Hsap\TARDBPScer\UAS.T:Avic\GFP-YFP.cEa
      Hsap\TARDBPUAS.YFP.cEa
      TDP-43WT
      (Manzo et al., 2019)
      TDPWT
      (Joardar et al., 2015)
      hTDP-43
      (Chou et al., 2015)
      hwt
      (Chou et al., 2015)
      Name Synonyms
      Saccharomyces cerevisiae UAS construct a of Estes
      Secondary FlyBase IDs
        References (11)