Deficiency in pulmonary surfactant proteins in mice with fatty acid binding protein 4‐<i>Cre</i>‐mediated knockout of the tuberous sclerosis complex 1 gene
Bibliographic record
Abstract
New findings What is the central question of this study? Does tuberous sclerosis complex 1–mammalian target of rapamycin (mTOR) signalling regulate the synthesis of surfactant proteins A and B and, if so, can this contribute to the postnatal death of Fabp4‐Tsc1 cKO mice? What is the main finding and its importance? Our study reveals a novel mechanism for the regulation of alveolar surfactant proteins. Tuberous sclerosis complex 1–mTOR signalling contributes to the regulation of synthesis of surfactant proteins A and B. Deficiency of tuberous sclerosis complex 1 in alveolar epithelial cells may contribute to the postnatal death of Fabp4‐Tsc1 cKO mice. Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as gene transcription and protein translation, in response to growth factors and nutrient signals. Originally designed to test the role of TSC1 in adipocyte function, mice in which the gene for TSC1 was specifically deleted by the fatty acid binding protein 4 (FABP4)‐ Cre ( Fabp4‐Tsc1 cKO mice) died prematurely within 48 h after birth. The Fabp4‐Tsc1 cKO mouse revealed a much smaller phenotype relative to the wild‐type littermates. Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of Fabp4‐Tsc1 cKO mice for up to 23 days. Both macroscopic and microscopic haemorrhages were observed in the lungs of Fabp4‐Tsc1 cKO mice, while other tissues showed no significant changes. Levels of surfactant proteins A and B demonstrated a significant decrease in the Fabp4‐Tsc1 cKO mice, which was rescued by maternal injection of rapamycin. Co‐localization of FABP4 or TSC1 with surfactant protein B was also detected in neonatal pulmonary tissues. Our study suggests that TSC1–mTORC1 may be critical for the synthesis of surfactant proteins A and B.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".