摘　要：上游开放阅读框（uORF）作为真核生物基因5′非翻译区（5′-UTR）的重要组成部分，近年来因其在基因表达调控中的重要作用而备受关注。但是，目前在鱼类中对uORF的研究相对匮乏。本研究利用CRISPR/Cas9基因编辑技术，针对斑马鱼生长激素受体（ghr）基因中的uORF进行敲除，以探究uORF去除后对ghr表达及斑马鱼生长发育的影响。通过构建ghr-uORF缺失的斑马鱼模型，我们发现敲除uORF后，ghr基因的mRNA和蛋白表达水平升高，且突变体斑马鱼在生长后期表现出生长优势。此外，突变体斑马鱼的肌肉组织发育也发生了变化，肌纤维形态接近圆形，排列较为紧密。这些结果表明，uORF在调控ghr基因表达中发挥了抑制作用，且敲除uORF可能促进斑马鱼的生长和肌肉发育。本研究为理解uORF在动物中的调控机制提供了新的视角，并为鱼类遗传改良提供了新的策略。
关键词：斑马鱼；生长激素受体基因；上游开放阅读框；基因编辑；生长发育
中图分类号：Q78　　　    　　  文献标志码：A　　　    　DOI：10.3969/j.issn.1007-7146.2025.01.005

Abstract: The upstream open reading frame (uORF) as an important component of the 5′ untranslated region (5′-UTR) of eukaryotic genes, has attracted much attention in recent years due to its significant role in gene expression regulation. However, research on uORF in fish is relatively scarce at present. In this study, using CRISPR/Cas9 gene editing technology, we targeted and knocked out the uORF in the zebrafish growth hormone receptor gene (ghr) to explore the impact of uORF removal on ghr expression and zebrafish growth and development. By constructing a zebrafish model with a ghr-uORF deletion, we found that after knocking out the uORF, the mRNA and protein expression levels of the ghr gene increased, and the mutant zebrafish showed a growth advantage at the later stages of growth. In addition, the muscle tissue development of the mutant zebrafish also changed, with muscle fiber morphology becoming more circular and arrangement being tighter. These results indicate that uORF plays a suppressive role in regulating ghr gene expression, and knocking out uORF may promote the growth and muscle development of zebrafish. This study provides a new perspective for understanding the regulatory mechanism of uORF in animals and offers a new strategy for genetic improvement in fish.
Key words: zebrafish; growth hormone receptor gene; upstream open reading frame; gene editing; growth and development
（Acta Laser Biology Sinica, 2025, 34(1): 036-044）