FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: muscular dystrophy, DAG1-related
Open Close
General Information
Name
muscular dystrophy, DAG1-related
FlyBase ID
FBhh0000192
Disease Ontology Term
Parent Disease
OMIM
Overview

In humans, multiple genes have been implicated in muscular dystrophy; in addition, in most cases, any specific gene is implicated in multiple forms of the disease. This report describes fly models of muscular dystrophy related to the gene dystroglycan 1, also known as dystrophin-associated glycoprotein (DAG1); the dystrophin-glycoprotein complex links the extracellular matrix and the cytoskeleton in the skeletal muscle. The DAG1 gene is implicated in several forms of muscular dystrophy, see MIM:128239 (see also FBhh0000207, FBhh0000208). There is a single fly ortholog, Dmel\Dg, for which classical hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

A UAS construct of the wild-type human Hsap\DAG1 gene has been introduced into flies; heterologous rescue has not been tested.

The more severe hypomorphic alleles of Dmel\Dg, when homozygous, are lethal in late larval stage; larval muscle phenotypes have been described. Precise levels of Dg appear to be critical: lower levels slow down neuronal stem cell division, while higher levels accelerate proliferation and perturb neuron differentiation. Animals with altered Dg levels, either loss- and gain-of-function mutants, exhibit a cobblestone brain phenotype (a type of lissencephaly). Adult phenotypes have allowed characterization of genetic interactions. Physical interactions of the Dg protein product have been described; see below and in the FlyBase gene report for Dg.

MicroRNAs of the mir-310 cluster (mir-310, mir-311, mir-312 and mir-313) bind to the extended 3'UTR of longer Dmel\Dg transcripts. Animals carrying a small deletion that removes all 4 genes of the mir-310 cluster exhibit a cobblestone brain phenotype.

[updated May 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: muscular dystrophy, DAG1-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of inherited muscle disorders. Muscle weakness typically presents from birth to early infancy. Affected infants typically appear "floppy" with low muscle tone and poor spontaneous movements. Affected children may present with delay or arrest of gross motor development together with joint and/or spinal rigidity. [Gene Reviews, Congenital Muscular Dystrophy Overview; 2019.05.31]

Genetics

A form of limb-girdle muscular dystrophy-dystroglycanopathy (type C9; MDDGC9) is caused by homozygous mutation in the gene encoding alpha-dystroglycan (DAG1). A second more severe type of muscular dystrophy (MIM:616538) is also associated with mutations in the DAG1 gene. [from MIM:613818, MIM:128239; 2016.03.11]

Cellular phenotype and pathology

The brain malformation cobblestone lissencephaly (type II lissencephaly) is observed in severe forms of α-dystroglycanopathy (Yamamoto, et al., 2014; pubmed:25403635).

Molecular information

Dystroglycan is a central component of the dystrophin-glycoprotein complex that links the extracellular matrix and the cytoskeleton in the skeletal muscle. [from Gene Cards, DAG1, 2016.03.25]

External links
Disease synonyms
cobblestone lissencephaly
LGMD2P
limb-girdle muscular dystrophy
limb-girdle muscular dystrophy-dystroglycanopathy
limb-girdle muscular dystrophy-dystroglycanopathy, type C9
lissencephaly, DAG1-related
lissencephaly type II
MDDGC9
muscular dystrophy-dystroglycanopathy (limb-girdle), type C9
α-dystroglycanopathies
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.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (5)
    Gene Snapshot
    Dystroglycan (Dg) encodes a major non-integrin extracellular matrix (ECM) receptor that connects the ECM to the actin cytoskeleton. It regulates animal survival and temperature preference, muscle integrity, myotendinous and neuromuscular junction formation and function, nervous system development, axon pathfinding, rhabdomere differentiation, neuronal stem cell division and epithelial polarity. [Date last reviewed: 2019-03-07]
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate-scoring ortholog of human DAG1 (1 Drosophila to 1 human). Dmel\Dg shares 23% identity and 36% similarity with the human gene.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Homologous to several human microRNAs, including MIR92A and MIR928 (FBrf0242402).

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        Homologous to the human microRNA MIR92A (FBrf0242402).

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Cellular component (GO)
          Gene Groups / Pathways
          Comments on ortholog(s)

          Homologous to several human microRNAs, including MIR92A, MIR928 and MIR25 (FBrf0242402).

          Orthologs and Alignments from DRSC
          DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
          Cellular component (GO)
            Gene Groups / Pathways
            Comments on ortholog(s)

            Homologous to several human microRNAs, including MIR92A and MIR25 (FBrf0242402).

            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 (68 groups)
              protein-protein
              Interacting group
              Assay
              References
              anti tag coimmunoprecipitation, western blot
              anti tag coimmunoprecipitation, western blot
              fluorescence polarization spectroscopy, predetermined participant
              anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry
              anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry
              proximity ligation assay, fluorescence microscopy
              anti tag coimmunoprecipitation, western blot
              anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot
              anti tag coimmunoprecipitation, anti tag western blot
              anti tag coimmunoprecipitation, anti tag western blot
              anti bait coimmunoprecipitation, western blot
              anti tag coimmunoprecipitation, anti tag western blot
              RNA-RNA
              Interacting group
              Assay
              References
              luminiscence technology, immunohistochemistry, quantitative reverse transcription pcr
              luminiscence technology
              luminiscence technology
              quantitative reverse transcription pcr, immunohistochemistry, luminiscence technology
              immunohistochemistry, luminiscence technology, quantitative reverse transcription pcr
              quantitative reverse transcription pcr, immunohistochemistry, luminiscence technology
              immunohistochemistry, quantitative reverse transcription pcr, luminiscence technology
              RNA-RNA
              Interacting group
              Assay
              References
              western blot, luminiscence technology
              luminiscence technology
              luminiscence technology
              quantitative reverse transcription pcr, immunohistochemistry, luminiscence technology
              luminiscence technology, quantitative reverse transcription pcr
              quantitative reverse transcription pcr, luminiscence technology
              luminiscence technology, necessary binding region, western blot
              luminiscence technology
              luminiscence technology, quantitative reverse transcription pcr
              fluorescence technology
              quantitative reverse transcription pcr, luminiscence technology
              RNA-protein
              Interacting group
              Assay
              References
              anti bait coimmunoprecipitation, northern blot
              RNA-RNA
              Interacting group
              Assay
              References
              luminiscence technology, western blot
              luminiscence technology
              luminiscence technology
              immunohistochemistry, luminiscence technology, quantitative reverse transcription pcr
              luminiscence technology, quantitative reverse transcription pcr
              quantitative reverse transcription pcr, luminiscence technology
              western blot, luminiscence technology, necessary binding region
              luminiscence technology
              luminiscence technology, quantitative reverse transcription pcr
              fluorescence technology
              quantitative reverse transcription pcr, luminiscence technology
              RNA-RNA
              Interacting group
              Assay
              References
              luminiscence technology, western blot
              fluorescence technology
              luminiscence technology
              luminiscence technology
              quantitative reverse transcription pcr, immunohistochemistry, luminiscence technology
              quantitative reverse transcription pcr, luminiscence technology
              fluorescence technology
              quantitative reverse transcription pcr, luminiscence technology
              luminiscence technology, necessary binding region, western blot
              luminiscence technology
              luminiscence technology, quantitative reverse transcription pcr
              fluorescence technology
              luminiscence technology, quantitative reverse transcription pcr
              RNA-protein
              Interacting group
              Assay
              References
              enzymatic study, autoradiography
              RNA-RNA
              Interacting group
              Assay
              References
              luminiscence technology, western blot
              luminiscence technology
              luminiscence technology
              immunohistochemistry, quantitative reverse transcription pcr, luminiscence technology
              quantitative reverse transcription pcr, luminiscence technology
              luminiscence technology, quantitative reverse transcription pcr
              western blot, luminiscence technology, necessary binding region
              luminiscence technology
              quantitative reverse transcription pcr, luminiscence technology
              luminiscence technology, quantitative reverse transcription pcr
              Alleles Reported to Model Human Disease (Disease Ontology) (14 alleles)
              Models Based on Experimental Evidence ( 7 )
              Modifiers Based on Experimental Evidence ( 5 )
              Allele
              Disease
              Interaction
              References
              Models Based on Experimental Evidence ( 2 )
              Modifiers Based on Experimental Evidence ( 0 )
              Allele
              Disease
              Interaction
              References
              Models Based on Experimental Evidence ( 1 )
              Modifiers Based on Experimental Evidence ( 0 )
              Allele
              Disease
              Interaction
              References
              Models Based on Experimental Evidence ( 1 )
              Modifiers Based on Experimental Evidence ( 0 )
              Allele
              Disease
              Interaction
              References
              Models Based on Experimental Evidence ( 1 )
              Allele
              Disease
              Evidence
              References
              Modifiers Based on Experimental Evidence ( 0 )
              Allele
              Disease
              Interaction
              References
              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
              Related mammalian, viral, bacterial, or synthetic 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
              Delta2-3 transposase
              piggyBac activity
              Delta2-3 transposase
              P-element activity
              ethyl methanesulfonate
              References (22)