Abnormal exocrine pancreas histology in NKCC1-deficient mice

The Na-K-2Cl cotransporter-1, NKCC1, is encoded by the SLC12A2 gene. Loss of function mutations in SLC12A2 in human patients have been link to multi-organ dysfunction including hearing impairment; cystic fibrosis-like disease, lung and intestinal disease linked to respiratory problems and mucus plugs, dysmorphic facial features, and severe neurodevelopmental disorder. Patients with complete loss of function mutation and the NKCC1-DFX patient suffered from pancreatic insufficiency requiring total parenteral nutrition to improve their quality of life. Here we report the pathology observed in the pancreas of NKCC1-KO mice. NKCC1-KO mice pancreas present a striking phenotype in the pancreas characterized by exocrine pancreas destruction, increased immune cell infiltrate and fibrosis. Acinar cell showed increased cell proliferation. NKCC1-KO mice pancreas show acini lumen obstruction due to mucus plugs and incomplete mucus release which accumulate in the subapical area of acinar cells. Staining with insulin and glucagon showed atrophy of the islet of Langerhans in NKCC1-KO mice compared to wild-type. The data demonstrate that pancreatic abnormalities exist the NKCC1-KO mice and that loss of function mutations in SLC12A2 likely contribute to the pancreatic insufficiency and chronic pancreatitis observed in human patients. NIH Grant to Eric Delpire •GM118944, DK093501 NIH Grants to VUMC Cell Imaging Shared Resource •CA68485, DK20593, DK58404, DK5963 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.