Intercalated Cell Claudin‐4 knockout mice display abnormal renal sodium and potassium conservation and hypercalciuria
Bibliographic record
Abstract
Distal Renal tubular acidosis is a disease characterized by the inability to acidify the urine below a pH of 5.5, metabolic acidosis, hypokalemia and hyperchloremia. It is caused by mutations in genes encoding the v‐B1‐H + ‐ATPase, the cytosolic carbonic anhydrase II or the kidney anion exchanger 1 (kAE1) in the renal collecting duct (CD). We recently discovered that kAE1 physically and functionally interacts with the tight junction protein claudin‐4 (Cldn‐4). This protein is expressed in principal (PC) and intercalated cells (IC) and forms a paracellular chloride pore and sodium barrier. With the aim to decipher the physiological role of the kAE1/Cldn‐4 interaction, we generated and characterized IC‐specific Cldn‐4 KO mouse. The knockout mice displayed a 30% reduction in Cldn‐4 abundance in isolated CD, in agreement with the reported IC/PC ratios. Although the KO animals developed normally and did not display an obvious phenotype, they presented a higher urinary calcium concentration at steady state than control animals. Feeding the mice a low NaCl diet caused the Cldn‐4 KO animals to have a more alkaline and dilute urine than control animals. Upon acid challenge, the Cldn‐4 KO mice excreted less urinary sodium and potassium compared with control animals. These results suggest that tight junction Cldn‐4 contributes to the maintenance of appropriate electrolyte and acid‐base balance. Support or Funding Information This work was funded by the Canadian Institutes of Health Research, the Kidney Foundation of Canada, the Women and Children's Health Research Institute (supported by the Stollery Children's Hospital Foundation), Alberta Innovates and the Canada Foundation for Innovation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".