Abstract
Introduction
Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children, and its cause is unknown. Recently, researchers have traced a defect in the gene CHD7 to AIS. CHD7 encodes for a chromodomain helicase of the DNA-binding domain protein family and is thought to have a crucial role in many basic cellular functions. However, the functional role of CHD7 in AIS is still elusive. In this study, we investigated the potential pathogenic effect of gene defects in CHD7 in vivo by evaluating their effect on spine formation and development in zebrafish.
Methods
To investigate the function of the CHD7 encoded protein, we generated an antisense morpholino oligonucleotide against the CHD7 gene to disrupt the translation of the gene transcripts and knockdown the levels of its protein. The morpholino was injected into single-cell stage zebrafish embryos. The injected fish were allowed to develop and were then assessed for distinct phenotypes reminiscent of scoliosis by histological stains.
Results
Knockdown of CHD7 resulted in a spectrum of ocular and heart anomalies. We noted that 26% of the zebrafish morphants exhibited curvature of the body axis at early stages. Histological stains of the vertebrae at later stages revealed that the spine of the zebrafish morphant had abnormal kinks rather than scoliotic curves. These defects were accompanied by reduced vertebral mineralisation around the kink area. The CHD7 morphant also showed severe cranial nerve abnormalities and had missing or malformed otolith—a part of the vestibular system analogous to the human ear.
Conclusions
Our findings indicate a key role of CHD7 in eye, heart, and ear development but not in the onset of skeletal deformities as observed in scoliosis. Our results are similar to the congenital abnormities associated with CHD7 mutations in the CHARGE syndrome.
Acknowledgments
This study is supported by the Yves Cotrel Fondation.
