Npt2 Gene Disruption Confers Resistance to the Inhibitory Action of Parathyroid Hormone on Renal Sodium-Phosphate Cotransport
Bibliographic record
Abstract
PTH inhibition of renal sodium-phosphate (Na-Pi) cotransport is associated with the endocytic retrieval of the type II Na-Pi cotransporter, Npt2, from the renal brush border membrane into the late endosomal/lysosomal compartment.The aim of the present study was to determine whether mice homozygous for the disrupted Npt2 gene (Npt2 Ϫ/Ϫ ) exhibit decreased renal Pi reabsorption in response to PTH.We demonstrate that PTH has no effect on the serum Pi concentration, fractional excretion of Pi, or Na-dependent Pi transport in renal brush border membrane vesicles in Npt2 Ϫ/Ϫ mice.In contrast, PTH elicits a fall in the serum Pi concentration, an increase in urinary Pi excretion, a decrease in brush border membrane Na-Pi cotransport, and a corresponding reduction in the relative abundance of Npt2 protein in wild-type mice (Npt2 ϩ/ϩ ).Both Npt2 Ϫ/Ϫ and Npt2 ϩ/ϩ mice exhibit a significant rise in the urinary cAMP/creatinine ratio in response to PTH, indicating that generalized resistance to PTH cannot account for the absence of the PTH response in Npt2 Ϫ/Ϫ mice.In addition, we demonstrate that Pi-depleted normal mice respond to PTH with a decrease in renal brush border membrane Na-Pi cotransport and Npt2 protein, indicating that Pi deficiency per se does not account for PTH resistance in Npt2 Ϫ/Ϫ mice.Taken together, our data provide compelling evidence that Npt2 gene expression is crucial for PTH effects on renal Pi handling.
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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 | 0.000 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".