斑马鱼生长激素受体基因上游开放阅读框敲除对生长发育影响的研究  

Investigation of the Impact of Upstream Open Reading Frame Knockout in the Growth Hormone Receptor Gene on the Growth and Development of Zebrafish

作　　者：王海涛 刘纯洁 赵凯月 符文 肖亚梅[1] 彭亮跃[1] WANG Haitao;LIU Chunjie;ZHAO Kaiyue;FU Wen;XIAO Yamei;PENG Liangyue(College of Life Sciences,Hunan Normal University,Changsha 410081,China)

机构地区：[1]湖南师范大学生命科学学院,长沙41001

出　　处：《激光生物学报》2025年第1期36-44,共9页Acta Laser Biology Sinica

基　　金：国家自然科学基金资助项目(32072959)。

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。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.

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 

分 类 号：Q78[生物学—分子生物学]