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General Information
Name
amyotrophic lateral sclerosis 1
FlyBase ID
FBhh0000019
Overview

This report describes amyotrophic lateral sclerosis 1 (ALS1), which is a subtype of amyotrophic lateral sclerosis. The human gene implicated in this disease is SOD1, which is a Cu-Zn superoxide dismutase. Most cases of SOD1-related familial ALS follow autosomal dominant inheritance; rare cases of autosomal recessive inheritance have been reported. There is one high-scoring fly ortholog of SOD1, Sod1, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

Multiple UAS constructs of the human gene Hsap\SOD1 have been introduced into flies, including wild-type SOD1 and genes carrying mutational lesions implicated in ALS1; phenotypes similar to aspects of the human disease are observed. Heterologous rescue (functional complementation) of some phenotypes of Dmel\Sod1 null mutants has been demonstrated.

Variant(s) implicated in human disease tested (as transgenic human gene, SOD1): the A4V, G37R, G41D, G85R, G93A, G93C, and I114T variant forms of the human gene have been introduced into flies. Variants implicated in ALS1 have been introduced into the endogenous Dmel\Sod1 locus via homologous recombination. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G36R in the fly Sod1 gene [corresponds to G37R (G38R) in the human SOD1 gene]; H47R in the fly Sod1 gene [corresponds to [H48R (H49R) in the human SOD1 gene]; H70Y in the fly Sod1 gene [corresponds to H71Y(H72Y) in the human SOD1 gene]; G84R in the fly Sod1 gene [corresponds to G85R (G86R) in the human SOD1 gene].

Animals homozygous for loss-of-function mutations in the Dmel\Sod1 gene (including alleles analogous to human variants that render the protein enzymatically inactive) exhibit phenotypes similar to the human disease, including neurodegeneration, locomotor deficits, and reduced lifespan. Physical interactions of the Dmel\Sod1 protein product have been described; see below and in the Sod1 gene report. Phenotypic assays using the fly gene have allowed characterization of genetic interactions.

[updated Jan. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: amyotrophic lateral sclerosis
Symptoms and phenotype

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996, pubmed:8875253). ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. [from OMIM:105400, 2015.02.11]

Specific Disease Summary: amyotrophic lateral sclerosis 1
OMIM report

[AMYOTROPHIC LATERAL SCLEROSIS 1; ALS1](https://omim.org/entry/105400)

Human gene(s) implicated

[DYNACTIN 1; DCTN1](https://omim.org/entry/601143)

[PERIPHERIN; PRPH](https://omim.org/entry/170710)

[SUPEROXIDE DISMUTASE 1; SOD1](https://omim.org/entry/147450)

[NEUROFILAMENT PROTEIN, HEAVY POLYPEPTIDE; NEFH](https://omim.org/entry/162230)

Symptoms and phenotype
Genetics

ALS1 is associated with mutations in the superoxide dismutase-1 gene (SOD1). Although most cases of SOD1-related familial ALS follow autosomal dominant inheritance, rare cases of autosomal recessive inheritance have been reported. [from OMIM:105400, 2015.02.12]

Cellular phenotype and pathology
Molecular information

The SOD1 gene encodes superoxide dismutase-1, a major cytoplasmic antioxidant enzyme that metabolizes superoxide radicals to molecular oxygen and hydrogen peroxide, thus providing a defense against oxygen toxicity (Niwa et al., 2007, pubmed:17666395). Soluble cytoplasmic SOD1 is a copper- and zinc-containing enzyme (Sherman et al., 1983, pubmed:6577438). [from OMIM:147450, 2015.02.12]

External links
Disease synonyms
ALS
ALS1
ALS-SOD1
amyotrophic lateral sclerosis
amyotrophic lateral sclerosis 1, autosomal dominant
amyotrophic lateral sclerosis 1, familial; FALS
amyotrophic lateral sclerosis 1; ALS1
amyotrophic lateral sclerosis type 1
FALS
fALS
familial amyotrophic lateral sclerosis
Lou Gehrig's disease
Lour Gehrig's disease
motor neurone disease
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 (See DIOPT, link below).

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Dmel\Sod shares 57% identity and 67% similarity with human SOD1.

    Ortholog of human SOD1 (1 Drosophila to 1 human).

    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 (41 groups)
      protein-protein
      Interacting group
      Assay
      References
      comigration in non denaturing gel electrophoresis, molecular weight estimation by staining
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      anti tag coimmunoprecipitation, peptide massfingerprinting
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      Alleles Reported to Model Human Disease (Disease Ontology) (21 alleles)
      Models Based on Experimental Evidence ( 9 )
      Modifiers Based on Experimental Evidence ( 11 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 5 )
      Modifiers Based on Experimental Evidence ( 5 )
      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
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      RNAi constructs available
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      Transgene
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      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      I-SceI
      I-SceI
      I-SceI
      I-SceI
      amorphic allele - molecular evidence
      CRISPR/Cas9
      amorphic allele - genetic evidence
      natural population
      amorphic allele - genetic evidence
      gamma ray
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      gamma ray
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      References (59)