Abstract
Trrap (transformation/transcription domain-associated protein) is a component shared by several histone acetyltransferase (HAT) complexes and participates in transcriptional regulation and DNA repair; however, the developmental functions of Trrap in vertebrates are not fully understood. Recently, it has been reported that human patients with genetic mutations in the TRRAP gene show various symptoms, including facial dysmorphisms, microcephaly and global developmental delay. To investigate the physiological functions of Trrap, we established trrap gene-knockout zebrafish and examined loss-of-function phenotypes in the mutants. The trrap zebrafish mutants exhibited smaller eyes and heads than the wild-type zebrafish. The size of the ventral pharyngeal arches was reduced and the mineralization of teeth was impaired in the trrap mutants. Whole-mount in situ hybridization analysis revealed that dlx3 expression was narrowly restricted in the developing ventral pharyngeal arches, while dlx2b expression was diminished in the trrap mutants. These results suggest that trrap zebrafish mutants are useful model organisms for a human disorder associated with genetic mutations in the human TRRAP gene.
Highlights
Trrap is a component shared by several histone acetyltransferase (HAT) complexes and participates in transcriptional regulation and DNA repair; the developmental functions of Trrap in vertebrates are not fully understood
The expression of trrap stained by the antisense trrap DIG RNA probe, but not the sense probe, was strongly detected in the head at 24 h post-fertilization, suggesting that the trrap gene is involved in craniofacial development
To investigate the function of the zebrafish trrap gene, we designed trrap-specific CRISPR RNAs targeting codon 1000 to disrupt the trrap gene and established trrap-knockout zebrafish with a 5-bp deletion that resulted in a frameshift mutation at the codon 1003 (Supplemental Fig. S1)
Summary
Trrap (transformation/transcription domain-associated protein) is a component shared by several histone acetyltransferase (HAT) complexes and participates in transcriptional regulation and DNA repair; the developmental functions of Trrap in vertebrates are not fully understood. Whole-mount in situ hybridization analysis revealed that dlx[3] expression was narrowly restricted in the developing ventral pharyngeal arches, while dlx2b expression was diminished in the trrap mutants These results suggest that trrap zebrafish mutants are useful model organisms for a human disorder associated with genetic mutations in the human TRRAP gene. RNA sequencing analysis revealed that skin fibroblasts from patients exhibit significant expression differences in several genes, suggesting the involvement of TRRAP in the transcriptional regulation of various genes Another group independently showed that the human TRRAP gene is responsible for autosomal dominant nonsyndromic hearing loss (ADNSHL)[6]. Demonstrated that the trrap-mutant zebrafish exhibited impairment of tooth mineralization and abnormally small eyes and head, and short ventral pharyngeal arches, which may be associated with the craniofacial abnormalities in human patients with TRRAP genetic mutations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
