常染色体显性软骨营养不良,Stickler2型和马歇尔综合征,以面部异常为特征,视力缺陷,听力损失,和由COL11A1突变引起的关节问题。斑马鱼携带两份Col11a1基因,命名为Col11a1a和Col11a1b。Col11a1a位于斑马鱼24号染色体上,Col11a1b位于斑马鱼2号染色体上。Col11a1a和Col11a1b的表达模式是不同的,并且Col11a1a与导致人常染色体软骨营养不良的COL11A1和导致软骨营养不良小鼠模型cho/cho变化的基因最相似。我们使用击倒方法研究了Col11a1a在斑马鱼颅面和轴向骨骼发育中的功能。击倒显示Meckel软骨异常,耳石,和整体身体长度。使用CRISPR/Cas9基因编辑方法观察到类似的表型,尽管与反义吗啉代寡核苷酸治疗的瞬时效应相比,CRISPR/Cas9效应更严重。这项研究的结果提供了证据,表明Col11a1a的斑马鱼基因是正常发育所必需的,并且具有与哺乳动物COL11A1基因相似的功能。由于其透明度,外部施肥,Col11a1a击倒,敲除斑马鱼模型系统可以,因此,有助于填补脊椎动物骨骼发育过程中早期事件的知识空白,这些知识在哺乳动物模型系统中不那么成立,并帮助我们了解Col11a1相关的早期发育事件。
The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and articular joint issues resulting from mutations in COL11A1. Zebrafish carry two copies of the Col11a1 gene, designated Col11a1a and Col11a1b. Col11a1a is located on zebrafish chromosome 24 and Col11a1b is located on zebrafish chromosome 2. Expression patterns are distinct for Col11a1a and Col11a1b and Col11a1a is most similar to COL11A1 that is responsible for human autosomal chondrodystrophies and the gene responsible for changes in the chondrodystrophic mouse model cho/cho. We investigated the function of Col11a1a in craniofacial and axial skeletal development in zebrafish using a knockdown approach. Knockdown revealed abnormalities in Meckel\'s cartilage, the otoliths, and overall body length. Similar phenotypes were observed using a CRISPR/Cas9 gene-editing approach, although the CRISPR/Cas9 effect was more severe compared to the transient effect of the antisense morpholino oligonucleotide treatment. The results of this study provide evidence that the zebrafish gene for Col11a1a is required for normal development and has similar functions to the mammalian COL11A1 gene. Due to its transparency, external fertilization, the Col11a1a knockdown, and knockout zebrafish model systems can, therefore, contribute to filling the gap in knowledge about early events during vertebrate skeletal development that are not as tenable in mammalian model systems and help us understand Col11a1-related early developmental events.