FB2025_01 , released February 20, 2025
Allele: Dmel\DCTN1-p150G38S
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General Information
Symbol
Dmel\DCTN1-p150G38S
Species
D. melanogaster
Name
FlyBase ID
FBal0277608
Feature type
allele
Associated gene
Dmel\DCTN1-p150
Associated Insertion(s)
Carried in Construct
Key Links
Genomic Maps

Allele class

hypomorphic allele - genetic evidence

hypomorphic allele - molecular evidence

Mutagen
Nature of the Allele
Allele class

hypomorphic allele - genetic evidence

(Lloyd et al., 2012)

hypomorphic allele - molecular evidence

(Lloyd et al., 2012)
Mutagen
ends-in gene targeting
(Lloyd et al., 2012)
I-CreI
(Lloyd et al., 2012)
FLPase
(Lloyd et al., 2012)
I-SceI
(Lloyd et al., 2012)
Progenitor genotype
Cytology
Description

Ends-in targeting at the Gl locus, followed by resolution of the resulting tandem duplication has resulted in a G38S amino acid replacement in Gl.

(Lloyd et al., 2012)
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
point_mutation
3L:13,929,960..13,929,960 [+]
Nucleotide change:

G13929960A

Amino acid change:

G38S | DCTN1-p150-PA

Reported amino acid change:

G38S

Comment:

Mutation in analogous codon in human DCTN implicated in HMN7B; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator based on reported amino acid change.

(Lloyd et al., 2012)
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  motor neuron disease
      CEA
      (Lloyd et al., 2012)
      Modifiers Based on Experimental Evidence ( 0 )
      Disease
      Interaction
      References
      Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
       

      The GlG38S mutation corresponds to a distal hereditary motor neuropathy-causing mutation in humans. The authors state that further analysis of adult GlG38S flies will be required to determine how well they model distal hereditary motor neuropathy pathologically, but that several of their findings indicate that this model does share features with human motor neuron diseases, including aggregation of mutant protein within motor neurons, adult-onset locomotor impairment, and a deficit in synaptic transmission at the NMJ.

      (Lloyd et al., 2012)
      Disease-implicated variant(s)
       
      This allele represents a human variant implicated in disease.
      (Lloyd et al., 2012)
      DCTN1:p.Gly59Ser
      (FlyBase curators, 2019-)
      Variants Synonym(s)
      DCTN1:p.Gly42Ser
      Associated human disease model(s)
      External database links
      ClinVar: DCTN1_8401
      Comments concerning this variant
      Phenotypic Data
      Phenotypic Class
      Phenotype Manifest In
      Detailed Description
      Statement
      Reference

      Homozygous and GlG38S/GlΔ22 larvae show normal locomotion, but adult homozygotes have dramatically impaired locomotor activity and are unable to fly. The animals develop progressive paralysis with age and have a dramatically reduced lifespan (median survival of 16 days) compared to wild type (median survival of 70 days).

      Homozygous larvae do not show a "tail-flip" or "axonal jam" phenotype.

      Mutant larvae show a decrease in the proportion of stationary endosomes when axonal endosomal transport is analysed, but all other axonal transport measures (including flux, velocity and processivity) are normal.

      GlG38S/GlΔ22 third instar larvae have a normal number of synaptic boutons per neuromuscular junction (NMJ) in proximal abdominal segments (A2 and A3) but show a small but significant increase in the number of synaptic boutons per NMJ in distal segments (A5 and A6). The terminal boutons (the distal-most synaptic boutons) are swollen at the mutant NMJ and show an approximately 2-fold increase in bouton volume in distal segments.

      Homozygous and GlG38S/GlΔ22 larvae show a significant reduction in the amplitude of the evoked junctional potential (EJP) at the NMJ compared to controls. The frequency and amplitude of spontaneous miniature EJPs is normal in homozygotes. Quantal content is reduced in homozygotes.

      (Lloyd et al., 2012)
      External Data
      Interactions
      Show genetic interaction network for Enhancers & Suppressors
      Phenotypic Class
      Other
      Statement
      Reference

      DCTN1-p150G38S, Khc[+]/Khc8 has lethal phenotype

      (Lloyd et al., 2012)
      Phenotype Manifest In
      Enhanced by
      Statement
      Reference

      DCTN1-p150G38S has NMJ bouton phenotype, enhanceable by Khc[+]/Khc8

      (Lloyd et al., 2012)

      DCTN1-p150G38S/DCTN1-p150Δ22 has phenotype, enhanceable by Khc[+]/Khc8

      (Lloyd et al., 2012)
      Additional Comments
      Genetic Interactions
      Statement
      Reference

      GlG38S/GlΔ22 ; Khc8/+ animals rarely survive to pupal stages.

      Khc8/+ enhances the swelling of the terminal boutons which is seen in GlG38S larvae.

      (Lloyd et al., 2012)
      Xenogenetic Interactions
      Statement
      Reference
      Complementation and Rescue Data
      Rescued by

      DCTN1-p150G38S is rescued by DCTN1-p150UAS.cLa/Scer\GAL4VGlut1-OK371

      (Lloyd et al., 2012)

      DCTN1-p150G38S/DCTN1-p150l1 is rescued by DCTN1-p150CH322-82J07

      (Lloyd et al., 2012)
      Partially rescued by

      DCTN1-p150G38S/DCTN1-p150l1 is partially rescued by DCTN1-p150UAS.cLa/Scer\GAL4T80

      (Lloyd et al., 2012)
      Comments

      Expression of GlScer\UAS.cLa under the control of Scer\GAL4T80 rescues the lethality of Gll1/GlG38S animals, although the rescued animals are sterile.

      Expression of GlCH322-82J07 fully rescues Gll1/GlG38S animals (the rescued animals are viable and fertile).

      Expression of GlScer\UAS.cLa under the control of Scer\GAL4VGlut-OK371 rescues the electrophysiological defects seen at the neuromuscular junction in GlG38S larvae.

      (Lloyd et al., 2012)
      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
      DCTN1-p150G38S
      GlG38S
      (Lloyd et al., 2012)
      Name Synonyms
      Secondary FlyBase IDs
        References (2)