Heterozygous mutation to <i>Chd8</i> causes macrocephaly and widespread alteration of neurodevelopmental transcriptional networks in mouse
Bibliographic record
Abstract
Summary The chromatin remodeling gene CHD8 represents a central node in early neurodevelopmental gene networks implicated in autism. We examined the impact of heterozygous germline Chd8 mutation on neurodevelopment in mice. Network analysis of neurodevelopmental gene expression revealed subtle yet strongly significant widespread transcriptional changes in Chd8 +/− mice across autism-relevant networks from neurogenesis to synapse function. Chd8 +/− expression signatures included enrichment of RNA processing genes and a Chd8-regulated module featuring altered transcription of chromatin remodeling, splicing, and cell cycle genes. Chd8 +/− mice exhibited increased proliferation during brain development and neonatal increase in cortical length and volume. Structural MRI confirmed regional brain volume increase in adult Chd8 +/− mice, consistent with clinical macrocephaly. Adult Chd8 +/− mice displayed normal social interactions, and repetitive behaviors were not evident. Our results show that Chd8 +/− mice exhibit neurodevelopmental changes paralleling CHD8 +/− humans and show that Chd8 is a global genomic regulator of pathways disrupted in neurodevelopmental disorders.
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 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".