PUBLICATION

A genetic model of CEDNIK syndrome in zebrafish highlights the role of the SNARE protein Snap29 in neuromotor and epidermal development

Authors
Mastrodonato, V., Beznoussenko, G., Mironov, A., Ferrari, L., Deflorian, G., Vaccari, T.
ID
ZDB-PUB-190206-10
Date
2019
Source
Scientific Reports   9: 1211 (Journal)
Registered Authors
Deflorian, Gianluca, Vaccari, Thomas
Keywords
none
MeSH Terms
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/physiology
  • Qc-SNARE Proteins/metabolism
  • Mutation
  • Protein Binding
  • Keratoderma, Palmoplantar/genetics
  • Keratoderma, Palmoplantar/metabolism*
  • Keratoderma, Palmoplantar/physiopathology
  • Phenotype
  • Qb-SNARE Proteins/metabolism
  • Zebrafish/metabolism
  • Synaptosomal-Associated Protein 25/metabolism
  • Synaptosomal-Associated Protein 25/physiology
  • Humans
  • SNARE Proteins/metabolism*
  • SNARE Proteins/physiology
  • Autophagy
  • Models, Genetic
  • Nervous System Malformations/metabolism
  • Membrane Fusion
  • Neurocutaneous Syndromes/genetics
  • Neurocutaneous Syndromes/metabolism*
  • Neurocutaneous Syndromes/physiopathology
  • Animals
(all 24)
PubMed
30718891 Full text @ Sci. Rep.
Abstract
Homozygous mutations in SNAP29, encoding a SNARE protein mainly involved in membrane fusion, cause CEDNIK (Cerebral Dysgenesis, Neuropathy, Ichthyosis and Keratoderma), a rare congenital neurocutaneous syndrome associated with short life expectancy, whose pathogenesis is unclear. Here, we report the analysis of the first genetic model of CEDNIK in zebrafish. Strikingly, homozygous snap29 mutant larvae display CEDNIK-like features, such as microcephaly and skin defects. Consistent with Snap29 role in membrane fusion during autophagy, we observe accumulation of the autophagy markers p62 and LC3, and formation of aberrant multilamellar organelles and mitochondria. Importantly, we find high levels of apoptotic cell death during early development that might play a yet uncharacterized role in CEDNIK pathogenesis. Mutant larvae also display mouth opening problems, feeding impairment and swimming difficulties. These alterations correlate with defective trigeminal nerve formation and excess axonal branching. Since the paralog Snap25 is known to promote axonal branching, Snap29 might act in opposition with, or modulate Snap25 activity during neurodevelopment. Our vertebrate genetic model of CEDNIK extends the description in vivo of the multisystem defects due to loss of Snap29 and could provide the base to test compounds that might ameliorate traits of the disease.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
io010
    Small Deletion
    rw0TgTransgenic Insertion
      sa13359
        Point Mutation
        1 - 3 of 3
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        Human Disease / Model
        Human Disease Fish Conditions Evidence
        CEDNIK syndromesnap29sa13359/sa13359standard conditionsTAS
        1 - 1 of 1
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        Sequence Targeting Reagents
        Target Reagent Reagent Type
        bdnfMO1-bdnfMRPHLNO
        snap29CRISPR2-snap29CRISPR
        snap29MO1-snap29MRPHLNO
        1 - 3 of 3
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        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-krtmonoclonal
          IgG2aMouse
          Ab10-sqstm1polyclonalRabbit
          1 - 2 of 2
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          Orthology
          Gene Orthology
          snap29
          1 - 1 of 1
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          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          1 - 1 of 1
          Show
          Mapping
          No data available