PUBLICATION

Multiple Developmental Defects in sox11a Mutant Zebrafish with Features of Coffin-Siris Syndrome

Authors
Jia, S., Wu, X., Wu, Y., Cui, X., Tao, B., Zhu, Z., Hu, W.
ID
ZDB-PUB-201020-32
Date
2020
Source
International journal of biological sciences   16: 3039-3049 (Journal)
Registered Authors
Hu, Wei, Zhu, Zuoyan
Keywords
CRISPR/Cas9, Coffin-Siris, sox11, zebrafish
MeSH Terms
  • Abnormalities, Multiple*/genetics
  • Animals
  • Face/abnormalities
  • Hand Deformities, Congenital*/genetics
  • Intellectual Disability
  • Mice
  • Micrognathism*/genetics
  • Neck/abnormalities
  • Zebrafish/genetics
PubMed
33061816 Full text @ Int. J. Biol. Sci.
Abstract
A previous study suggested that human Coffin-Siris syndrome is related to the mutation of SOX11. Since the homozygous SOX11 mutant mice died soon after birth, no suitable model was available for the study of the pathogenic mechanism of Coffin-Siris syndrome. To solve this problem, we generated two viable homozygous zebrafish mutants, sox11am/m and sox11bm/m . We found that the sox11am/m mutant possessed Coffin-Siris syndrome features. The sox11am/m mutants exhibited growth deficiency from 3.3 hpf embryos to adulthood. Furthermore, the sox11am/m mutant also displayed microcephaly, narrow pupillary distance, achondroplasia, and bone deformity in adults. Growth deficiency could be rescued by the injection of sox11a mRNA at the one-cell stage. In addition, the expression levels of genes related to cartilage and bone were downregulated in the sox11am/m mutant, indicating that sox11a mainly affected the growth and development of zebrafish by regulating the expression of genes related to skeletal development. Our results indicate that sox11am/m mutant zebrafish offered a potential model system to help with the search for pathogenic mechanisms of human Coffin-Siris syndrome.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping