Polymorphisms in 5′UTR of ENaC α, β and γgenes in Dahl and Wistar rats
Bibliographic record
Abstract
The activity of the epithelial sodium channel (ENaC) in the kidney is elevated in salt sensitive (SS) versus salt resistant (SR) Dahl rats. Blockade of ENaC in the brain by benzamil prevents the increase in BP in SS Dahl rats on high salt diet. Previously, we did a comprehensive screening of the complete coding regions of ENaC α, β and γ genes and no differences were identified in SS versus SR Dahl rats. In the presentstudy, we assessed whether the promotor regions of ENaC genes might harbor genetic variation(s) that enhance ENaC expression and contribute to salt sensitivity in Dahl SS, but not SR rats. Methods Screening 5′UTR of ENaC genes in Dahl SS, SR and control Wistar rats by Denaturing High Performance Liquid Chromatography (DHPLC) and automatic sequencing. Results Screening 2.2, 1.5, and 2.2 kb of 5′UTR of ENaCα, β and γ respectively showed no differences between Dahl SS and SR rats. A total of 18 SNPs; 4 SNPs in ENaCα 5′UTR, 2 in ENaCβ5′UTR, and 12 in ENaCγ 5′UTR were identified in Dahl SS and SR rats. 4 of these 18 SNPs were previously identified in the genome database of Brown Norway rats. The remaining 14 SNPs are novel polymorphisms. Of these 14 SNPs, 13 were also identified in Wistar rats. None of the identified SNPs in the 5′UTR of ENaC genes were located within the previously reported regulatory element DNA consensus sequences. Conclusions The first comprehensive screening of ENaC genes 5′UTR did not reveal any differences between SS and SR. Therefore, we could not link differences in activity of ENaC in SS versus SR to differences in ENaC 5′UTR sequences. The identified variations in ENaC genes 5′UTR on their own can not explain salt‐sensitive hypertension in Dahl SS rats.
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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".