Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus
Why this work is in the frame
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Bibliographic record
Abstract
The bHLH-PAS transcription factor SIM1 is required for the development of the paraventricular nucleus (PVN) of the hypothalamus. Mice homozygous for a null allele of Sim1 (Sim1(-/-)) lack a PVN and die perinatally. In contrast, we show here that Sim1 heterozygous mice are viable but develop early-onset obesity, with increased linear growth, hyperinsulinemia and hyperleptinemia. Sim1(+/-) mice are hyperphagic but their energy expenditure is not decreased, distinguishing them from other mouse models of early-onset obesity such as deficiencies in leptin and melanocortin receptor 4. Quantitative histological comparison with normal littermates showed that the PVN of Sim1(+/-) mice contains on average 24% fewer cells without a selective loss of any identifiable major cell type. Since acquired lesions in the PVN also induce increased appetite without a decrease in energy expenditure, we propose that abnormalities of PVN development cause the obesity of Sim1(+/-) mice. Severe obesity was described recently in a patient with a balanced translocation disrupting SIM1. Pathways controlling the development of the PVN thus have the potential to cause obesity in both mice and humans.
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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 it