Human HNF1B mRNA

Annular pancreas (AP) is a congenital pancreatic anomaly that causes acute abdominal pain and vomiting after birth. However, the genetic etiology of AP is still unclear, and no studies have reported AP in patients with 17q12 duplications. This study retrospectively analyzed the next-generation sequencing (NGS) data of individuals with 17q12 duplications from January 2016 to June 2020. To determine the function of HNF1B, a key gene in the 17q12 duplication region, the researchers microinjected human HNF1B mRNA into LiPan zebrafish transgenic embryos. A total of 19 cases of 17q12 duplication were confirmed. Among them, 4 patients (21.1%) were diagnosed with AP during exploratory laparotomy. Other common features of 17q12 duplications include intellectual disability (50%), gross motor development delay (50%), and epileptic seizures/seizures (31.58%). In the HNF1B overexpression model, the proportion of zebrafish pancreatic abnormalities was significantly increased. In summary, this study is the first to report the presence of AP in patients with duplications in the 17q12 region, leading to the phenotype of 17q12 duplication syndrome. In addition, zebrafish studies have confirmed the role of the HNF1B gene in pancreatic development.

Human HNF1B mRNA was microinjected into the pancreatic exocrine layer of 1-cell stage LiPan transgenic embryos at a dose of 50 pg/embryo. Embryos not injected with GFP mRNA and embryos injected with GFP mRNA were used as controls. Compared with the control group, the morphology of the pancreatic exocrine layer in the HNF1B overexpression group was significantly affected. The head of the zebrafish pancreas in the control group was larger, and the posterior tail extended to the end of the yolk sac. However, the zebrafish pancreas exocrine part in the HNF1B overexpression group showed abnormal morphology such as short pancreas, irregular shape or fuzzy shape (Figure 1A). This study analyzed the proportion of zebrafish with abnormal pancreatic exocrine part and the length of the pancreas. The results showed that the proportion of zebrafish with abnormal pancreatic exocrine part in the HNF1B overexpression group was significantly higher than that in the control group (Figure 1B), and the pancreas length was significantly lower than that in the control group (Figure 1C).

Figure 1. (A) Different characteristics of zebrafish in the HNF1B overexpression group and the control group. (B) The proportion of zebrafish with pancreatic abnormalities in the HNF1B overexpression group and the control group. (C) The length of the pancreas in the HNF1B overexpression group and the control group. (Xiao F, et al., 2021)