Abstract
CHARGE syndrome patients present features of idiopathic scoliosis in over 60% of cases, reduced bone mineral density and in a few cases osteopenia. While several clinical cases and studies regarding the spinal deformities in CHARGE syndrome bearing CHD7 mutations are well-documented, the underlying mechanisms remain elusive. Here, we detect and quantitatively analyze skeletal abnormalities in adult and young chd7−/− larvae.
We show that young chd7−/− larvae present with scoliosis and kyphosis already at 9 dpf. Gene expression analysis confirmed the reduction of osteoblast markers and Pparγ targets. MicroCT analyses identified abnormal Weberian apparatus structure and vertebral body morphology in chd7−/− mutants, with highly mineralized inclusions, along with variances in bone mineral density and bone volume. Additionally, we detect a specific depletion of Col2a1a in the zebrafish vertebral cartilage, in line with a significantly reduced number of chondrocytes.
Our study is the first to elucidate the mechanisms underlying morphological changes in vertebrae of adult chd7−/− zebrafish and decreased spinal integrity. The chd7−/− zebrafish will be beneficial in future investigations of the underlying pathways of spinal deformities in CHARGE syndrome.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of Interest
The authors declare no conflicts of interest
