Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & College of Fisheries, Key Laboratory of Freshwater Fish Reproduction and Development, Key Laboratory of Aquatic Sciences of Chongqing, Southwest University, Ministry of Education, Chongqing, 402460, China.
Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation of Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China.
Mar Biotechnol (NY). 2024 Oct;26(5):917-930. doi: 10.1007/s10126-024-10329-5. Epub 2024 Jun 11.
Traf6, an adaptor protein, exhibits non-conventional E3 ubiquitin ligase activity and was well studied as an important factor in immune systems and cancerogenesis. In mice, the traf6-null caused a perinatal death, so that the underlying pathophysiology of traf6-defeciency is still largely unclear in animals. Here, in the present study, a traf6 knockout zebrafish line (traf6) was generated and could survive until adulthood, providing a unique opportunity to demonstrate the functions of traf6 gene in animals' organogenesis beyond the mouse model. The body of traf6 fish was found to be significantly shorter than that of the wildtype (WT). Likewise, a comparative transcriptome analysis showed that 866 transcripts were significantly altered in the traf6 liver, mainly involved in the immune system, metabolic pathways, and progesterone-mediated oocyte maturation. Especially, the mRNA expression of the pancreas duodenum homeobox protein 1 (pdx1), glucose-6-phosphatase (g6pcb), and the vitellogenesis genes (vtgs) were significantly decreased in the traf6 liver. Subsequently, the glucose was found to be accumulated in the traf6 liver tissues, and the meiotic germ cell was barely detected in traf6 testis or ovary. The findings of this study firstly implied the pivotal functions of traf6 gene in the liver and gonads' development in fish species.
Traf6,一种衔接蛋白,表现出非传统的 E3 泛素连接酶活性,作为免疫系统和癌症发生的重要因素而得到了深入研究。在小鼠中, traf6 缺失会导致围产期死亡,因此 traf6 缺陷的潜在病理生理学在动物中仍很大程度上不清楚。在这里,在本研究中,产生了 traf6 敲除斑马鱼系(traf6),其能够存活到成年期,为在动物器官发生中展示 traf6 基因的功能提供了独特的机会,超出了小鼠模型。发现 traf6 鱼的身体明显短于野生型(WT)。同样,比较转录组分析表明, traf6 肝脏中有 866 个转录本发生显著改变,主要涉及免疫系统、代谢途径和孕酮介导的卵母细胞成熟。特别是,胰腺十二指肠同源盒蛋白 1(pdx1)、葡萄糖-6-磷酸酶(g6pcb)和卵黄发生基因(vtgs)的 traf6 肝脏中的 mRNA 表达显著降低。随后发现 traf6 肝脏组织中葡萄糖积累, traf6 睾丸或卵巢中几乎检测不到减数分裂生殖细胞。这项研究的结果首次暗示了 traf6 基因在鱼类肝脏和性腺发育中的关键作用。