Caspase 3 Deficiency Rescues Peripheral Nervous System Defect in Retinoblastoma Nullizygous Mice
Bibliographic record
Abstract
The retinoblastoma tumor suppressor protein, pRb, is a key regulator of cell cycle and has been implicated in the terminal differentiation of neuronal cells. Mice nullizygous for pRb die by embryonic day 14.5 from hematopoietic and neurological defects attributed to failed differentiation (Clarke et al., 1992; Jacks et al., 1992; Lee et al., 1992). Previous studies by MacLeod et al. (1996) have demonstrated that the loss of p53 protects Rb-deficient CNS neurons but not peripheral nervous system (PNS) neurons from cell death. Thus, the mechanisms by which PNS neurons undergo apoptosis in response to Rb deficiency remain unknown. In view of the pivotal role of caspase 3 in the regulation of neuronal apoptosis during development, we examined its function in the execution of the wide-spread neuronal cell death induced by Rb deficiency. Our results support a number of conclusions. First, we show that caspase 3 becomes activated in all neuronal populations undergoing apoptosis. Second, caspase 3 deficiency does not extend the life span of Rb null embryos, because double null mutants exhibit high rates of liver apoptosis resulting in erythropoietic failure. Third, Rb/caspase 3 double-mutant neurons of the CNS exhibit widespread apoptosis similar to that seen in Rb mutants alone; thus caspase 3 deficiency does not protect this population from apoptosis. Finally, in contrast to the CNS, neurons of the PNS including those comprising the trigeminal ganglia and the dorsal root ganglia are protected from apoptosis in Rb/caspase 3 double-mutant embryos. Examination of the mechanistic differences between these two cell types suggest that CNS neurons may invoke other caspases to facilitate apoptosis in the absence of caspase 3. These findings suggest that PNS neurons are dependent on caspase 3 for the execution of apoptosis and that caspase 3 may serve as a key therapeutic target for neuroprotection after injury of this cell type.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".