Cerebral Vascular Abnormalities in a Murine Model of Hereditary Hemorrhagic Telangiectasia
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: Hereditary hemorrhagic telangiectasia type 1 (HHT1) is an autosomal dominant vascular dysplasia caused by mutations in the endoglin gene and characterized by dilated vessels and arteriovenous malformations (AVMs). To understand the etiology of this disorder, we evaluated the cerebral vasculature of endoglin heterozygous (Eng+/-) mice, which represent the only animal model of HHT1. METHODS: The cerebral vasculature of Eng+/- and Eng+/+ mice from C57BL/6 (B6) and 129/Ola (129) strains with a differential susceptibility to HHT1 was studied with corrosion casting. Casts were observed by scanning electron microscopy to detect malformations and evaluate arterial diameters and orientation of endothelial nuclei. Measurements were taken to assess relative constriction at arteriolar branching points and downstream relative dilatation. RESULTS: Three of 10 Eng+/- mice demonstrated abnormal vascular findings including AVMs, while none of 15 Eng+/+ mice did. The incidence of relative constriction at arteriolar branching points was significantly less in both Eng+/- groups than in their Eng+/+ counterparts. The occurrence of relative dilatation was significantly greater in B6-Eng+/- than in B6-Eng+/+ mice. Endothelial nuclei were significantly rounder and deviated more from the direction of blood flow in Eng+/- than in Eng+/+ mice. CONCLUSIONS: Eng+/- mice showed significant structural alterations in cerebral blood vessels, indicating that the level of endoglin on endothelium is critical for maintenance of normal vasculature. Since endoglin haploinsufficiency is associated with HHT1, such changes in arteriolar structures might occur in HHT1 patients and predispose them to AVMs and their sequelae.
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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 | 0.000 |
| 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 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".