Brain‐Specific <i>Gata4</i> Downregulation in <i>Greywick</i> Female Mice Models the Metabolic Subtype of Polycystic Ovary Syndrome
Bibliographic record
Abstract
Polycystic ovary syndrome (PCOS) is a heterogenous disorder characterized by reproductive and metabolic abnormalities. PCOS etiology remains poorly understood, although the hypothalamus is suspected to play a central role in many cases. Human genetic studies have also shown an association with the transcription factor-coding gene GATA4, but without providing a functional link. Here, we show that adult Greywick female mice may bridge this gap. These mice phenocopy PCOS with partial penetrance, due to the serendipitous insertion of a Gata4 promoter-driven transgene in a strong enhancer region. Resulting robust transgene expression in subsets of hypothalamic neurons and glia impairs endogenous Gata4 expression, resulting in misexpression of genes linked to the control of fertility and food intake. We also show that this previously overlooked role of GATA4 in the hypothalamus can be replicated by conditional knockout approaches. Overall, this study sheds light not only on PCOS etiology but also on the role played by GATA4 in the central control of reproduction.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".