The NFATc2 transcription factor is required for normal heart function and signaling in adult mice
Bibliographic record
Abstract
The Ca2+- dependent phosphatase, calcineurin (Cn) and its downstream transcriptional effectors, nuclear factor of activated T-cells (NFAT), are major intracellular modulators of cardiac hypertrophy. In young mice, transcription factor NFATc2 has been identified as the major NFAT isoform responsible for Cn-mediated cardiac hypertrophy. We observed that 7–9 month old NFATc2−/− mice have a higher susceptibility to cardiac dilatation and sudden death, prompting us to monitor changes in heart morphology and growth pathways in this model. Using histology, we show that hearts of adult NFATc2−/− mice display a more dilated left ventricle and thinner interventricular wall. In addition, NFATc2 null hearts have increased GATA-4 expression, higher nuclear transit of GATA-4 and NFATc1, and decreased GSK3-β expression, thus supporting the finding that adult NFATc2−/− mice are more prone to heart failure. Furthermore, angiotensin II-induced cardiac growth reveals that hearts of NFATc2−/− mice hypertrophy to the same extent as wild-type mice, display a thinner myocardial wall and have decreased active AKT and eIF2α expression, suggesting altered translational regulation of myocardial growth. Our collective results propose an uncharacterized role of NFATc2 for normal heart function and growth signaling in adult mice, providing evidence of Cn-signaling being crucial at later stages of life. Supported by CIHR, NSERC and CRC to RNM.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".