A novel role for the «Ostm1» Osteopetrotic gene in neuronal homeostasis
Bibliographic record
Abstract
Osteopetrosis is a genetic disease characterized by an excess of bone resulting from a defect in the bone resorbing osteoclasts. The discovery by our lab of the Osteopetrosis associated transmembrane protein 1 (Ostm1) gene responsible for the most severe recessive osteopetrosis in both grey-lethal (gl/gl) mice and humans provides us with the unique opportunity to decipher the role of this novel protein in a normal and pathological context. Functional rescue was undertaken by directing Ostm1 expression in multiple hematopoietic lineages including osteoclasts with a PU1-Ostm1-BAC transgene. These mice show complete rescue of the standard bone and hematopoietic osteopetrotic phenotypes however they still die prematurely. Knowing Ostm1 is highly expressed in brain tissue, we hypothesized that death was associated with CNS defects. These mice consistently display a severe neurodegenerative phenotype with stimulation of autophagy. To demonstrate the functional link of Ostm1 with the CNS we developed mouse models targeting Ostm1 to neuronal cells and astrocytes by using the specific Synapsin and GFAP promoters respectively. By rescue of neurodegeneration in these gl/gl transgenic mice using the Synapsin promoter, we established a major role for Ostm1 in neuronal cells independent of the hematopoietic and osteoclast defects.
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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) | 0.000 | 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) | 0.003 | 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".