Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas.
Bibliographic record
Abstract
Activation of the p21-ras signaling pathway from aberrantly expressed receptors promotes the growth of malignant human astrocytomas. We developed a transgenic mouse astrocytoma model using the glial fibrillary acidic protein (GFAP) promoter to express oncogenic V(12)Ha-ras, specifically in astrocytes. The development of GFAP-immunoreactive astrocytomas was directly proportional to the level of V(12)Ha-ras transgene expression. Chimeras expressing high levels of V(12)Ha-ras in astrocytes died from multifocal malignant astrocytomas within 2 weeks, whereas those with moderate levels went to germ-line transmission. Ninety-five percent of these mice died from solitary or multifocal low- and high-grade astrocytomas within 2-6 months. These transgenic astrocytomas are pathologically similar to human astrocytomas, with a high mitotic index, nuclear pleomorphism, infiltration, necrosis, and increased vascularity. Derivative astrocytoma cells are tumorigenic upon inoculation in another host. The transgenic astrocytomas exhibit additional molecular alterations associated with human astrocytomas, including a decreased or absent expression of p16, p19, and PTEN as well as overexpression of EGFR, MDM2, and CDK4. Cytogenetic analysis revealed consistent clonal aneuploidies of chromosomal regions syntenic with comparable loci altered in human astrocytomas. Therefore, this transgenic mouse astrocytoma model recapitulates many of the molecular histopathological and growth characteristics of human malignant astrocytomas in a reproducible, germ-line-transmitted, and high-penetrance manner.
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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 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".