Orthopedic Surgery and Trauma Center, Pitié-Salpêtrière Teaching Hospital, 47 Boulevard de l'Hôpital, 75013, Paris, France.
Paris Brain Institute, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, 75013, Paris, France.
Sci Rep. 2021 Apr 1;11(1):7392. doi: 10.1038/s41598-021-86856-1.
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, cfap298. The zebrafish mutant line cfap298, 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 cfap298 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 cfap298 scoliotic individuals display a typical AIS phenotype, with orthopedic criteria mirroring patient's diagnosis.
脑脊液（CSF）循环依赖于在脑和脊髓腔管腔中突出的运动纤毛的跳动。纤毛运动相关基因的突变会扰乱脑脊液循环，并导致幼年斑马鱼出现脊柱侧凸样畸形。然而，这些脊柱排列缺陷尚未通过用于诊断青少年特发性脊柱侧凸（AIS）的临床标准得到验证。本研究的目的是使用矫形标准描述靶向纤毛极性和运动相关基因 cfap298 的 AIS 斑马鱼突变模型的脊柱畸形。由于纤毛运动缺陷导致 CSF 流动改变的 cfap298 斑马鱼突变系被饲养至幼年期。对突变动物的分析基于微计算机断层扫描（micro-CT），在 QUANTUM FX CALIPER 上进行，使用 59 µm-30 mm 协议。在分析的 cfap298 斑马鱼中，有 63%呈现出脊柱的三维畸形，在幼年期期间具有进展性，在雌性中更为常见，表现为右侧凸、旋转成分，并至少涉及一处脱位。我们在此证实 cfap298 脊柱侧凸个体表现出典型的 AIS 表型，其矫形标准反映了患者的诊断。
