Amhr2-Cre–Mediated Global Tspo Knockout
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Although the role of translocator protein (TSPO) in cholesterol transport in steroid-synthesizing cells has been studied extensively, recent studies of TSPO genetic depletion have questioned its role. Amhr2-Cre mice have been used to generate Leydig cell-specific Tspo conditional knockout (cKO) mice. Using the same Cre line, we were unable to generate Tspo cKO mice possibly because of genetic linkage between Tspo and Amhr2 and coexpression of Amhr2-Cre and Tspo in early embryonic development. We found that Amhr2-Cre is expressed during preimplantation stages, resulting in global heterozygous mice (gHE; Amhr2-Cre+/–,Tspo–/+). Two gHE mice were crossed, generating Amhr2-Cre–mediated Tspo global knockout (gKO; Tspo–/–) mice. We found that 33.3% of blastocysts at E3.5 to E4.5 showed normal morphology, whereas 66.7% showed delayed development, which correlates with the expected Mendelian proportions of Tspo+/+ (25%), Tspo–/– (25%), and Tspo+/– (50%) genotypes from crossing 2 Tspo–/+ mice. Adult Tspo gKO mice exhibited disturbances in neutral lipid homeostasis and reduced intratesticular and circulating testosterone levels, but no change in circulating basal corticosterone levels. RNA-sequencing data from mouse adrenal glands and lungs revealed transcriptome changes in response to the loss of TSPO, including changes in several cholesterol-binding and transfer proteins. This study demonstrates that Amhr2-Cre can be used to produce Tspo gKO mice instead of cKO, and can serve as a new global “Cre deleter.” Moreover, our results show that Tspo deletion causes delayed preimplantation embryonic development, alters neutral lipid storage and steroidogenesis, and leads to transcriptome changes that may reflect compensatory mechanisms in response to the loss of function of TSPO.
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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 | 0.001 |
| 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