Cerebrospinal fluid (CSF) circulation relies on the beating of motile cilia projecting in the lumen of the brain and spinal cord cavities Mutations in genes involved in cilia motility disturb cerebrospinal fluid circulation and result in scoliosis-like deformities of the spine in juvenile zebrafish. However, these defects in spine alignment have not been validated with clinical criteria used to diagnose adolescent idiopathic scoliosis (AIS). The aim of this study was to describe, using orthopaedic criteria the spinal deformities of a zebrafish mutant model of AIS targeting a gene involved in cilia polarity and motility, cfap298tm304. The zebrafish mutant line cfap298tm304, exhibiting alteration of CSF flow due to defective cilia motility, was raised to the juvenile stage. The analysis of mutant animals was based on micro-computed tomography (micro-CT), which was conducted in a QUANTUM FX CALIPER, with a 59 µm-30 mm protocol. 63% of the cfap298tm304 zebrafish analyzed presented a three-dimensional deformity of the spine, that was evolutive during the juvenile phase, more frequent in females, with a right convexity, a rotational component and involving at least one dislocation. We confirm here that cfap298tm304 scoliotic individuals display a typical AIS phenotype, with orthopedic criteria mirroring patient’s diagnosis.

Scheuermann’s disease, also referred to as Scheuermann’s kyphosis, is the second most frequent spine deformity occurring in humans after adolescent idiopathic scoliosis (AIS), both with an unclear etiology. Recent genetic studies in zebrafish unraveled new mechanisms linked to AIS, highlighting the role of the Reissner fiber, an acellular polymer bathing in the cerebrospinal fluid (CSF) in close proximity with ciliated cells and mechanosensory neurons lining the central canal of the spinal cord (CSF-cNs). However, while the Reissner fiber and ciliary beating have been linked to AIS-like phenotypes in zebrafish, the relevance of the sensory functions of CSF-cNs for human spine disorders remains unknown. Here, we show that the thoracic hyper-kyphosis of the spine previously reported in adult pkd2l1 mutant zebrafish, in which the mechanosensory function of CSF-cNs is likely defective, is restricted to the sagittal plane and is not associated with vertebral malformations. By applying orthopedic criteria to analyze the amplitude of the curvature at the apex of the kyphosis, the curve pattern, the sagittal balance and sex bias, we demonstrate that pkd2l1 knock-outs develop a phenotype reminiscent of Scheuermann’s disease. Altogether our work consolidates the benefit of combining genetics and analysis of spine deformities in zebrafish to model idiopathic spine disorders in humans.