PT  - JOURNAL ARTICLE
AU  - Breuer, Maximilian
AU  - Rummler, Maximilian
AU  - Zaouter, Charlotte
AU  - Willie, Bettina M.
AU  - Patten, Shunmoogum A.
TI  - Altered vertebrae morphology and bone mineralization in a zebrafish model of CHARGE syndrome
AID  - 10.1101/2020.07.10.197533
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.10.197533
4099  - http://biorxiv.org/content/early/2020/07/11/2020.07.10.197533.short
4100  - http://biorxiv.org/content/early/2020/07/11/2020.07.10.197533.full
AB  - 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 StatementThe authors have declared no competing interest.