Targeted mutation of NaV1.4 causes paralysis in mouse as observed in attacks of Hyperkalemic Periodic Paralysis (HyperKPP)
Bibliographic record
Abstract
The single point mutation M1592V on the skeletal muscle sodium channel, NaV1.4, causes human HyperKPP. For this specific point mutation, the onset of the paralytic attacks occurs between 5–10 years of age. In response to several known triggers, such attacks may then increase in frequency, duration and intensity until adolescence, but typically they diminish in mid‐ adulthood. By that time, fixed muscle weakness and a major shift toward type I and IIA fibers are observed in many muscles. The objective of this study was to determine if introducing a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene (mice (+/M1592V) ) encoding the skeletal muscle voltage‐gated Na+ channel NaV1.4 also may predispose to paralytic attacks with changes in frequency and intensity. Paralysis of the hindlimb muscles were observed during the period of 6‐12 weeks postnatal. By 8 weeks of age, EDL muscle from mice (+/M1592V) had more than 2‐fold less type IIB and 2‐times more type IIA fibers when compared to EDL muscles of wild type mice. Finally, measurement of NaV1.4 content by immunohistochemistry showed a small decrease in protein content from 3 to 8 weeks of age followed by no further changes up to 16 weeks of age. More importantly, there was no difference in NaV1.4 protein content between wild type and mice (+/M1592V) . We conclude that altered mouse NaV1.4 equivalent to the human M1592V mutation causes paralytic attacks during a postnatal window of 6–12 weeks and a shift toward type IIA fibers that is not associated with a change in NaV1.4 protein content.
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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 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.003 | 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".