The Musculoskeletal Genetics Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Department of Orthopedics, University of Colorado, Aurora, CO, USA.
Curr Osteoporos Rep. 2023 Dec;21(6):650-659. doi: 10.1007/s11914-023-00831-5. Epub 2023 Nov 16.
GWAS, as a largely correlational analysis, requires in vitro or in vivo validation. Zebrafish (Danio rerio) have many advantages for studying the genetics of human diseases. Since gene editing in zebrafish has been highly valuable for studying embryonic skeletal developmental processes that are prenatally or perinatally lethal in mammalian models, we are reviewing pros and cons of this model.
The true power for the use of zebrafish is the ease by which the genome can be edited, especially using the CRISPR/Cas9 system. Gene editing, followed by phenotyping, for complex traits such as BMD, is beneficial, but the major physiological differences between the fish and mammals must be considered. Like mammals, zebrafish do have main bone cells; thus, both in vivo stem cell analyses and in vivo imaging are doable. Yet, the "long" bones of fish are peculiar, and their bone cavities do not contain bone marrow. Partial duplication of the zebrafish genome should be taken into account. Overall, small fish toolkit can provide unmatched opportunities for genetic modifications and morphological investigation as a follow-up to human-first discovery.
全基因组关联分析（GWAS）主要是一种相关性分析，需要进行体外或体内验证。斑马鱼（Danio rerio）在研究人类疾病的遗传学方面有许多优势。由于斑马鱼中的基因编辑对于研究哺乳动物模型中胚胎骨骼发育过程具有重要价值，这些过程在产前或围产期是致命的，因此我们正在回顾该模型的优缺点。
使用斑马鱼的真正优势在于可以轻松编辑基因组，特别是使用 CRISPR/Cas9 系统。对于 BMD 等复杂性状，进行基因编辑，然后表型分析是有益的，但必须考虑鱼类和哺乳动物之间的主要生理差异。与哺乳动物一样，斑马鱼确实有主要的骨细胞；因此，既可以进行体内干细胞分析，也可以进行体内成像。然而，鱼类的“长”骨是特殊的，其骨腔不含有骨髓。应该考虑到斑马鱼基因组的部分重复。总的来说，小鱼工具包可以为遗传修饰和形态学研究提供无与伦比的机会，作为人类首次发现的后续研究。
