Urinary Sodium Wasting and Disrupted Collecting Duct Function in Mice with dRTA-Causing <i>SLC4A1</i> Mutations
Bibliographic record
Abstract
Abstract Distal renal tubular acidosis (dRTA) results in metabolic acidosis due to impaired urinary acidification and can also result in an unexplained urinary sodium-wasting phenotype. Here, we report the generation and characterization of a novel dRTA mutant mouse line, Ae1 L919X knockin (KI). Homozygous L919X KI mice exhibit typical dRTA features including a reduced ability to acidify urine in response to an acid load. This renal acidification defect was associated with a reduced number of Ae1-positive type A intercalated cells. To assess whether these mice exhibit urinary sodium-wasting as seen in some dRTA patients, homozygous KI L919X and the previously described R607H KI mice were fed a salt-depleted acid diet. In line with human patients, both mouse strains exhibited urinary sodium loss. Additionally, we identified increased expression of tight junction proteins claudin-4 and -10b, suggesting a compensatory paracellular pathway in the loop of Henle. Consistent with data from human patients, L919X KI mice displayed a milder phenotype than R607H KI mice. Our findings reveal that both mouse strains are appropriate models for dRTA with a urinary salt-wasting phenotype and a compensatory up-regulation of the paracellular pathway in the ascending limb of the loop of Henle.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".