Pervasive cortical and white matter anomalies in a mouse model for <scp>CHARGE</scp> syndrome
Bibliographic record
Abstract
CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth, Genital anomalies and Ear abnormalities) syndrome is a disorder caused by mutations in the gene encoding CHD7, an ATP dependent chromatin remodelling factor, and is characterised by a diverse array of congenital anomalies. These include a range of neuroanatomical comorbidities which likely underlie the varied neurodevelopmental disorders associated with CHARGE syndrome, which include intellectual disability, motor coordination deficits, executive dysfunction, and autism spectrum disorder. Cranial imaging studies are challenging in CHARGE syndrome patients, but high-throughput magnetic resonance imaging (MRI) techniques in mouse models allow for the unbiased identification of neuroanatomical defects. Here, we present a comprehensive neuroanatomical survey of a Chd7 haploinsufficient mouse model of CHARGE syndrome. Our study uncovered widespread brain hypoplasia and reductions in white matter volume across the brain. The severity of hypoplasia appeared more pronounced in posterior areas of the neocortex compared to anterior regions. We also perform the first assessment of white matter tract integrity in this model through diffusion tensor imaging (DTI) to assess the potential functional consequences of widespread reductions in myelin, which suggested the presence of white matter integrity defects. To determine if white matter alterations correspond to cellular changes, we quantified oligodendrocyte lineage cells in the postnatal corpus callosum, uncovering reduced numbers of mature oligodendrocytes. Together, these results present a range of promising avenues of focus for future cranial imaging studies in CHARGE syndrome patients.
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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".