ArticleClinical science (London, England : 1979)2020
An inducible intestinal epithelial cell-specific NHE3 knockout mouse model mimicking congenital sodium diarrhea.
Article in Clinical science (London, England : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Sex differences in renal acid-base regulation.Current opinion in nephrology and hypertension · 2026Review
- Renal NHE3 is required to limit hypokalemia and metabolic acidosis during dietary potassium deficiency.Pflugers Archiv : European journal of physiology · 2026Article
- Mechanism of reduced intestinal phosphate absorption by tenapanor: a hypothesis.Clinical kidney journal · 2026Review
- Differential regulation of NHE3 expression in type 1 and type 2 diabetic intestine: impaired endosomal regulation of NHE3 expression in type 1 diabetes.American journal of physiology. Cell physiology · 2025Article
- Differential Regulation of NHE3 Expression in Type 1 and Type 2 Diabetic Intestine: Impaired Endosomal Regulation of NHE3 Expression in Type 1 Diabetes.bioRxiv : the preprint server for biology · 2025Article
- Vitamin DScientific reports · 2024Article
- New functions and roles of the NaPflugers Archiv : European journal of physiology · 2024Review
- Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.PloS one · 2024Article
- Intestinal Permeability, Irritable Bowel Syndrome with Constipation, and the Role of Sodium-Hydrogen Exchanger Isoform 3 (NHE3).Clinical and experimental gastroenterology · 2024Review
- Kidney and blood pressure regulation-latest evidence for molecular mechanisms.Clinical kidney journal · 2023Review
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Human Colonoid-Myofibroblast Coculture for Study of Apical NaInternational journal of molecular sciences · 2023Article
- Zinc Laurate Protects against Intestinal Barrier Dysfunction and Inflammation Induced by ETEC in a Mice Model.Nutrients · 2022Article
- The NHE3 Inhibitor Tenapanor Prevents Intestinal Obstructions in CFTR-Deleted Mice.International journal of molecular sciences · 2022Article
- Further delineation of SLC9A3-related congenital sodium diarrhea.Molecular genetics & genomic medicine · 2022Article
- NHE3 in the thick ascending limb is required for sustained but not acute furosemide-induced urinary acidification.American journal of physiology. Renal physiology · 2022Article
- Review
- Enhanced phosphate absorption in intestinal epithelial cell-specific NHE3 knockout mice.Acta physiologica (Oxford, England) · 2022Article
- Intestine-Specific NHE3 Deletion in Adulthood Causes Microbial Dysbiosis.Frontiers in cellular and infection microbiology · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The sodium-hydrogen exchanger isoform 3 (NHE3, SLC9A3) is abundantly expressed in the gastrointestinal tract and is proposed to play essential roles in Na+ and fluid absorption as well as acid-base homeostasis. Mutations in the SLC9A3 gene can cause congenital sodium diarrhea (CSD). However, understanding the precise role of intestinal NHE3 has been severely hampered due to the lack of a suitable animal model. To navigate this problem and better understand the role of intestinal NHE3, we generated a tamoxifen-inducible intestinal epithelial cell-specific NHE3 knockout mouse model (NHE3IEC-KO). Before tamoxifen administration, the phenotype and blood parameters of NHE3IEC-KO were unremarkable compared with control mice. After tamoxifen administration, NHE3IEC-KO mice have undetectable levels of NHE3 in the intestine. NHE3IEC-KO mice develop watery, alkaline diarrhea in combination with a swollen small intestine, cecum and colon. The persistent diarrhea results in higher fluid intake. After 3 weeks, NHE3IEC-KO mice show a ∼25% mortality rate. The contribution of intestinal NHE3 to acid-base and Na+ homeostasis under normal conditions becomes evident in NHE3IEC-KO mice that have metabolic acidosis, lower blood bicarbonate levels, hyponatremia and hyperkalemia associated with drastically elevated plasma aldosterone levels. These results demonstrate that intestinal NHE3 has a significant contribution to acid-base, Na+ and volume homeostasis, and lack of intestinal NHE3 has consequences on intestinal structural integrity. This mouse model mimics and explains the phenotype of individuals with CSD carrying SLC9A3 mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.