GSE134334
Deficiency in Ybx1 Leads to Postnatal Lethality and IBD-like Disease in Zebrafish
Y box-binding protein 1 (Ybx1) is critical for embryogenesis and organogenesis. In zebrafish, we identify Ybx1 is predominantly expressed in the enterocytes of intestine in day5 larvae, whereas its immediately degradation driven by ubiquitination on day6. Here we show the maternal lethality with cardiac edema in ybx1-/- larvae, and postnatal larval lethality exhibited in ybx1-/- larvae within the death window from 10dpf to 20dpf. To study the underlying mechanisms for the ybx1-/- larvae partial lethality, we performed RNA-seq and experimental results showed the increased ROS might be the underlying cause for the postnatal lethality. By ascorbic acid treatment, we found ascorbic acid exposure prevented ybx1-/- larvae from postnatal lethality, while hydrogen peroxide aggravated ybx1-/- larvae postnatal lethality during the death window. By RNA-seq analysis, we also found significantly increased expressions of mmp9 and mmp13a in ybx1-/- larvae, and by inhibition of either MMP9 or MMP13a expression partially rescue the ybx1-/- postnatal lethality during the death window. Later, we further identify the intestinal impairs on 30 dpf and further deteriorated severe intestinal disorder in Ybx1 deficiency zebrafish. By exposure of ybx1-/- zebrafish for 14 days, we discover ascorbic acid partially mend the impaired intestine in ybx1-/-. In this study, we demonstrate that ybx1-/- larvae were ROS-susceptible, and the increased inflammation in ybx1-/- larvae intestine identified enables the ybx1-/- zebrafish as good model for studying of intestinal disease. Overall design: three different genotypes, day5 WT, day6 WT, and day5 ybx1-/- were used total RNA extraction.