Loss of <scp>RNASEK</scp> Terminates Egg Cylinder Development by Impairing Lysosomal Function Associated With V‐ <scp>ATPase</scp> in Mouse
Bibliographic record
Abstract
ABSTRACT Although RNASEK is defined as a subunit of V‐ATPase, how it regulates the V‐ATPase and relevant physiological functions remains largely uncharacterized. Utilizing a homozygous RNASEK knockout mouse, we demonstrate that the null function of RNASEK leads to catastrophic developmental failure at the egg cylinder stage (E5.5). Rnasek −/− embryos exhibit pronounced lysosomal dysfunction and multilineage proliferation arrest, accompanied by the hallmarks of senescence, including elevated p21, reduced Ki67 and EdU incorporation as well as increased γH2AX foci, which are evident in vitro embryo culture as well. Unexpectedly, despite increased V0/V1 subunit colocalization, lysosomal alkalization, proteolytic failure, and autophagic flux blockade collectively indicate that the loss of RNASEK promotes malfunctional V‐ATPase assembly. Pharmacological restoration of lysosomal acidity via EN6 partially mitigates senescence and extends the developmental window. These findings demonstrate that RNASEK regulates lysosomal function via V‐ATPase and is required for egg cylinder development in the mouse embryo. Loss of RNASEK promotes premature senescence of multiple cell lineages, terminating early embryonic development.
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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 | 0.001 | 0.001 |
| 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".