ZFIN ID: ZDB-PUB-161030-8
Characterization of Zebrafish Models of Marinesco-Sjögren Syndrome
Kawahara, G., Hayashi, Y.K.
Date: 2016
Source: PLoS One   11: e0165563 (Journal)
Registered Authors: Kawahara, Genri
Keywords: Embryos, Zebrafish, Morpholino, Eyes, Eye muscles, Purkinje cells, Immunohistochemistry techniques, Muscle proteins
MeSH Terms:
  • Animals
  • Apoptosis
  • Autophagy
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Endoplasmic Reticulum Stress
  • Eye/pathology
  • Gene Expression Regulation
  • Guanine Nucleotide Exchange Factors/genetics
  • Muscle, Skeletal/metabolism
  • Phenotype
  • Purkinje Cells/pathology
  • Spinocerebellar Degenerations/drug therapy
  • Spinocerebellar Degenerations/genetics*
  • Spinocerebellar Degenerations/metabolism
  • Spinocerebellar Degenerations/pathology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
PubMed: 27792754 Full text @ PLoS One
SIL1 is a nucleotide exchange factor for the endoplasmic reticulum chaperone, BiP. Mutations in the SIL1 gene cause Marinesco-Sjögren syndrome (MSS), an autosomal recessive disease characterized by cerebellar ataxia, mental retardation, congenital cataracts, and myopathy. To create novel zebrafish models of MSS for therapeutic drug screening, we analyzed phenotypes in sil1 knock down fish by two different antisense oligo morpholinos. Both sil1 morphants had abnormal formation of muscle fibers and irregularity of the myosepta. Moreover, they showed smaller-sized eyes and loss of purkinje cells in cerebellar area compared to controls. Immunoblotting analysis revealed increased protein amounts of BiP, lipidated LC3, and caspase 3. These data supported that the sil1 morphants can represent mimicking phenotypes of human MSS. The sil1 morphants phenocopy the human MSS disease pathology and are a good animal model for therapeutic studies.