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

A previous study suggested that human Coffin-Siris syndrome is related to the mutation of . Since the homozygous 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, and . We found that the mutant possessed Coffin-Siris syndrome features. The mutants exhibited growth deficiency from 3.3 hpf embryos to adulthood. Furthermore, the mutant also displayed microcephaly, narrow pupillary distance, achondroplasia, and bone deformity in adults. Growth deficiency could be rescued by the injection of mRNA at the one-cell stage. In addition, the expression levels of genes related to cartilage and bone were downregulated in the mutant, indicating that mainly affected the growth and development of zebrafish by regulating the expression of genes related to skeletal development. Our results indicate that mutant zebrafish offered a potential model system to help with the search for pathogenic mechanisms of human Coffin-Siris syndrome.