Open Close
General Information
Name
epilepsy, refractory, SCN-alpha-ABCC1 model
FlyBase ID
FBhh0001134
Disease Ontology Term
Parent Disease
OMIM
Overview

A well-studied model of epilepsy in Drosophila makes use of mutant alleles of the fly gene para, which encodes a sodium voltage-gated channel alpha subunit (see 'epilepsy, SCN-alpha-related' FBhh0000289). This model has been used to assess therapeutic pharmaceuticals and drug regimens. A Drosophila model of refractory epilepsy has been created by combining this SCN-alpha-related model of epilepsy with pan-neuronal expression of ABCC1, a human gene involved in multi-drug resistance; ABCC1 (previously MRP1) has been found to be overexpressed in the neurons and glia of patients with refractory epilepsy.

In Drosophila, there is a single high-scoring ortholog of ABCC1, Dmel\MRP; the Drosophila gene has not been used in the context of this disease model.

Pan-neuronal expression of the human gene, Hsap\ABCC1, in the SCN-alpha (Dmel\para) model results in resistance to two antiepileptic drugs tested (sodium phenytoin and valproic acid).

[updated Nov. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: epilepsy, refractory, SCN-alpha-ABCC1 model
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Patients are considered to have refractory epilepsy if disabling seizures continue despite appropriate trials of two antiseizure drugs, either alone or in combination (Engel, 2014; pubmed:24791078).

Genetics
Cellular phenotype and pathology
Molecular information

The extrusion of anticancer drugs by members of the ATP-binding cassette (ABC) transporter family is one of the most widely recognized mechanisms of multidrug resistance (Fletcher et al., 2016; pubmed:27180306 ).

ABCC1 encodes a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra-and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance; it functions as a multispecific organic anion transporter. [Gene Cards, ABCC1; 2019.11.05]

ATP Binding Cassette (ABC) transporters form a special family of membrane proteins, characterized by homologous ATP-binding, and large, multispanning transmembrane domains. Several members of this family are primary active transporters, which significantly modulate the absorption, metabolism, cellular effectivity and toxicity of pharmacological agents (Glavinas et al., 2004; pubmed:16305368).

ABCC1 (MRP1) has been found to be overexpressed in the neurons and astrocytes of patients with refractory epilepsy (Sun et al., 2016; pubmed:26000815).

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila (reciprocal best hits); multiple related genes in both species.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    paralytic (para) is an essential gene required for locomotor activity. It encodes an α-subunit of voltage-gated sodium channels. It is required for generation of sodium-dependent action potentials. [Date last reviewed: 2019-03-14]
    Gene Groups / Pathways
    Comments on ortholog(s)

    Highest-scoring fly ortholog for human voltage-gated sodium channel alpha subunits encoded by ten different genes, including several associated with forms of epilepsy (SCN1A, SCN2A, SCN8A, SCN9A). Dmel\para shares 44-46% identity and 61-62% similarity with these human genes.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (2 groups)
      RNA-protein
      Interacting group
      Assay
      References
      pull down, anti tag western blot, anti tag coimmunoprecipitation, quantitative reverse transcription pcr
      anti tag coimmunoprecipitation, quantitative reverse transcription pcr
      Alleles Reported to Model Human Disease (Disease Ontology) (9 alleles)
      Models Based on Experimental Evidence ( 8 )
      Modifiers Based on Experimental Evidence ( 6 )
      Allele
      Disease
      Interaction
      References
      ameliorates  epilepsy
      model of  epilepsy
      model of  epilepsy
      is ameliorated by parats1
      is ameliorated by parats115
      is ameliorated by paraGD3392
      is ameliorated by parabss1
      is exacerbated by paraGEFS+
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      amorphic allele - molecular evidence
      FLPase
      amorphic allele - genetic evidence
      phiC31 integrase
      amorphic allele - genetic evidence
      PM hybrid dysgenesis
      ethyl methanesulfonate
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      amorphic allele - genetic evidence
      ends-out gene targeting
      ends-out gene targeting
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      phiC31 integrase
      References (4)