Fus在斑马鱼生长发育及两性生长异形中的功能

FUS IS ESSENTIAL FOR SOMATIC GROWTH AND SEXUAL SIZE DIMORPHISM IN ZEBRAFISH

  • 摘要: 为研究肉瘤融合基因(fus)在鱼类中的功能, 在斑马鱼中利用CRISPR/Cas9基因突变技术使fus基因产生移码突变。fus-/-纯合突变体斑马鱼发育正常并且完全可育, 但体长和体重在幼鱼和成年阶段都小于野生型斑马鱼。此外, 相较于野生型斑马鱼, fus-/-纯合突变体斑马鱼不存在雌鱼身体比例大于雄鱼的性别异形现象。在fus-/-纯合突变体斑马鱼早期幼鱼发育阶段, 一些生长相关基因包括gh1、ghraigf1、igf2astat5.1和socs6的表达水平显著低于野生型斑马鱼但其运动能力并未受到影响。因此, 不同于fus基因在哺乳动物中的功能, 它在斑马鱼中不参与运动神经元的发育, 但在调节鱼类躯体生长发育与两性生长异形方面有着重要的功能。

     

    Abstract: The Fused in sarcoma gene (FUS) is a RNA-binding protein implicated in the regulation of transcription and pre-mRNA splicing. Mutations in FUS lead to neurodegenerative diseases including ALS (amyotrophic lateral sclerosis) in mammals. However, little is known about fus function in fish species. Here, we generated frame-shift alleles in the zebrafish fus gene using CRISPR/Cas9 mutagenesis. Homozygous fus-/- zebrafish developed normally and were fully fertile, except that their body size and body weight were smaller than that of wild-type zebrafish at both the larvae and adult stages. In addition, the female-biased sexual size dimorphism in adult zebrafish was also eliminated when fus was mutated. The expression levels of several growth-related genes including gh1, ghra, igf1, igf2a, stat5.1 and socs6 were significantly reduced in fus-/- zebrafish larvae compared with the wild-type. However, there was no effect on locomotor activity in fus-/- zebrafish. Therefore, different from its functions in mammals, fus is not associated with motoneuron development and has a divergent function in regulating somatic growth and sexual size dimorphism in fish species.

     

/

返回文章
返回