RRC ID 59973
著者 Mastrodonato V, Beznoussenko G, Mironov A, Ferrari L, Deflorian G, Vaccari T.
タイトル A genetic model of CEDNIK syndrome in zebrafish highlights the role of the SNARE protein Snap29 in neuromotor and epidermal development.
ジャーナル 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.
巻・号 9(1)
ページ 1211
公開日 2019-2-4
DOI 10.1038/s41598-018-37780-4
PII 10.1038/s41598-018-37780-4
PMID 30718891
PMC PMC6361908
MeSH Animals Autophagy Humans Keratoderma, Palmoplantar / genetics Keratoderma, Palmoplantar / metabolism* Keratoderma, Palmoplantar / physiopathology Membrane Fusion Models, Genetic Mutation Nervous System Malformations / metabolism Neurocutaneous Syndromes / genetics Neurocutaneous Syndromes / metabolism* Neurocutaneous Syndromes / physiopathology Phenotype Protein Binding Qb-SNARE Proteins / metabolism Qc-SNARE Proteins / metabolism SNARE Proteins / metabolism* SNARE Proteins / physiology Synaptosomal-Associated Protein 25 / metabolism Synaptosomal-Associated Protein 25 / physiology Zebrafish / metabolism Zebrafish Proteins / metabolism* Zebrafish Proteins / physiology
IF 4.011
引用数 2
リソース情報
ゼブラフィッシュ Tg(CM-isl1:GFP)rw0