ArticleProceedings of the National Academy of Sciences of the United States of America2010
Claudin-2-deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 287 citations in OpenAlex.
- Inflammation-Induced Claudin-2 Up-Regulation Limits Pancreatitis Development by Enhancing Pancreatic Ductal Transport.Gastroenterology · 2026Article
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- Transcriptomic landscape reveals segment-specific molecular mechanisms underlying honeycomb-enhanced egg quality in laying hens.Poultry science · 2026Article
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- Stability and Robustness of a Generalized Pump-Leak Model for Epithelial Vesicles.Bulletin of mathematical biology · 2026Article
- Age- and Sex-dependent Effects of High-fructose, High-fat Diets on Small Bowel Inflammation and Hepatic Steatosis in F344 Rats.Journal of neurogastroenterology and motility · 2025Article
- Biology of calcium homeostasis regulation in intestine and kidney.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Claudin-2 enhances human antibody-mediated complement-dependent cytotoxicity of porcine endothelial cells by modulating antibody binding and complement activation.Frontiers in immunology · 2025Article
- Claudin-12: guardian of the tissue barrier or friend of tumor cells.Tissue barriers · 2025Review
- Paracellular Transport and Renal Tubule Calcium Handling: Emerging Roles in Kidney Stone Disease.Journal of the American Society of Nephrology : JASN · 2024Review
- The role of the mucosal barrier system in maintaining gut symbiosis to prevent intestinal inflammation.Seminars in immunopathology · 2024Review
- Inhibition of pannexin-1 does not restore electrolyte balance in precystic Pkd1 knockout mice.Physiological reports · 2024Article
- Claudin-2 upregulation enhances intestinal permeability, immune activation, dysbiosis, and mortality in sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Claudin-2 Mediates the Proximal Tubular Epithelial Cell-Fibroblast Crosstalk via Paracrine CTGF.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- The role of claudins in homeostasis.Nature reviews. Nephrology · 2023Review
- Article
- P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium.Communications biology · 2023Article
- Mechanisms of cerebrospinal fluid and brain interstitial fluid production.Neurobiology of disease · 2023Review
- Paracellular permeability and tight junction regulation in gut health and disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- Expression of Cell-Adhesion Molecules inInternational journal of molecular sciences · 2023Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Claudin-2 is highly expressed in tight junctions of mouse renal proximal tubules, which possess a leaky epithelium whose unique permeability properties underlie their high rate of NaCl reabsorption. To investigate the role of claudin-2 in paracellular NaCl transport in this nephron segment, we generated knockout mice lacking claudin-2 (Cldn2(-/-)). The Cldn2(-/-) mice displayed normal appearance, activity, growth, and behavior. Light microscopy revealed no gross histological abnormalities in the Cldn2(-/-) kidney. Ultrathin section and freeze-fracture replica electron microscopy revealed that, similar to those of wild types, the proximal tubules of Cldn2(-/-) mice were characterized by poorly developed tight junctions with one or two continuous tight junction strands. In contrast, studies in isolated, perfused S2 segments of proximal tubules showed that net transepithelial reabsorption of Na(+), Cl(-), and water was significantly decreased in Cldn2(-/-) mice and that there was an increase in paracellular shunt resistance without affecting the apical or basolateral membrane resistances. Moreover, deletion of claudin-2 caused a loss of cation (Na(+)) selectivity and therefore relative anion (Cl(-)) selectivity in the proximal tubule paracellular pathway. With free access to water and food, fractional Na(+) and Cl(-) excretions in Cldn2(-/-) mice were similar to those in wild types, but both were greater in Cldn2(-/-) mice after i.v. administration of 2% NaCl. We conclude that claudin-2 constitutes leaky and cation (Na(+))-selective paracellular channels within tight junctions of mouse proximal tubules.
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