Target deletion of the bifunctional type 12 17β-hydroxysteroid dehydrogenase in mice results in reduction of androgen and estrogen levels in heterozygotes and embryonic lethality in homozygotes
Bibliographic record
Abstract
17β-Hydroxysteroid dehydrogenases (17β-HSDs) are enzymes issued from convergent evolution of activity from various ancestral genes having different functions. Type 12 17β-HSD (17β-HSD12) was described as a bifunctional enzyme, involved in the biosynthesis of estradiol (E2) and the elongation of very long chain fatty acid (VLCFA). It catalyzes selectively the transformation of estrone (E1) into estradiol (E2) in human and primates, whereas in the mouse and Caenorhabditis elegans the enzyme catalyzes the 17β-reduction of both androgens and estrogens. It is also able to catalyze the reduction of 3-keto-acylCoA into 3-hydroxy-acylCoA in the elongation cycle of VLCFA biosynthesis. To further understand the physiological role of 17β-HSD12, we performed targeted disruption of the Hsd17b12 gene by substituting exons 8 and 9 that contain the active site with a neomycin cassette. The data indicate that heterozygous (HSD17B12+/-) mice are viable with reduced levels of sex steroids, whereas homozygous (HSD17B12-/-) mice show embryonic lethality. The present data are in agreement with the bifunctional activities of 17β-HSD12 suggesting that the VLCFA elongation activity, having its origin in the yeast, is most probably responsible for embryonic lethality in HSD17B12-/-, whereas the more recently acquired 17β-HSD12 activity is responsible for reduced sex steroid levels in HSD17B12+/-.
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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 | 0.001 |
| 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".