Dominant-negative β1 integrin mice have region-specific myelin defects accompanied by alterations in MAPK activity
Bibliographic record
Abstract
Recent studies have demonstrated the importance of beta1 integrin in oligodendrocyte maturation in vitro. Similar studies in vivo have been difficult due to the embryonic and perinatal lethality of null mutations in integrin subunits. Here, we have generated transgenic mouse models that overexpress full length beta1 integrin or express a dominant-negative beta1 integrin DeltaC (lacking the C-terminal tail) under the control of the proteolipid protein (PLP) promoter. We demonstrate that these transgenes are expressed predominantly in CNS tissues and more specifically in oligodendrocytes. Further analysis reveals that the dominant-negative beta1 integrin DeltaC transgenic mice, but not the full length beta1 integrin mice, have hypomyelinated axons in spinal cords and optic nerves. In addition, there is a significant increase in the number of unmyelinated axons within the spinal cords and optic nerves of the beta1 integrin DeltaC mice. In contrast, the corpus callosum from these mice did not show similar myelin defects. To assess if remyelination would be affected in the corpus callosum, mice were subjected to a cuprizone-induced demyelination. Interestingly, the dominant-negative mice recovered from this insult in a manner similar to the wild type littermates. Axons within the corpus callosum that were remyelinated had normal g-ratios; however, the actual percentage of myelinated axons was significantly reduced compared with wild type mice. We also show that the defects observed in the dominant-negative beta1 integrin DeltaC mice are accompanied by disruption of the MAP-kinase signaling pathway. Our work highlights the importance of beta1 integrin-mediated signaling in CNS myelination in vivo.
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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 | 0.000 | 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 | 0.001 |
| 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".