Novel Loss-of-Function Variant in HNF1a Induces β-Cell Dysfunction through Endoplasmic Reticulum Stress.

ABSTRACT: Heterozygous variants in the hepatocyte nuclear factor 1a (HNF1a) cause MODY3 (maturity-onset diabetes of the young, type 3). In this study, we found a case of novel HNF1a p.Gln125* (HNF1a-Q125ter) variant clinically. However, the molecular mechanism linking the new HNF1a variant to impaired islet β-cell function remains unclear. Firstly, a similar HNF1a-Q125ter variant in zebrafish (hnf1a^+/-) was generated by CRISPR/Cas9. We further crossed hnf1a^+/- with several zebrafish reporter lines to investigate pancreatic β-cell function. Next, we introduced HNF1a-Q125ter and HNF1a shRNA plasmids into the Ins-1 cell line and elucidated the molecular mechanism. hnf1a^+/- zebrafish significantly decreased the β-cell number, insulin expression, and

SUBMITTER: Chen Y 

PROVIDER: S-EPMC9656704 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature