Microarray analysis of gene expression in the cyclooxygenase knockout mice – a connection to autism spectrum disorder
Bibliographic record
Abstract
Abstract The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid‐signalling molecules such as prostaglandin E2 (PGE2) play an important role in healthy brain development. Abnormalities along the COX‐PGE2 signalling pathway due to genetic or environmental causes have been linked to autism spectrum disorder (ASD). This study aims to evaluate the effect of altered COX‐PGE2 signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase‐1 and cyclooxygenase‐2 (COX‐1−/− and COX‐2−/−) as potential model systems of ASD. Microarray analysis was used to determine global changes in gene expression during embryonic days 16 (E16) and 19 (E19). Gene Ontology: Biological Process (GO:BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to identify affected developmental genes and cellular processes. We found that in both knockouts the brain at E16 had nearly twice as many differentially expressed genes, and affected biological pathways containing various ASD‐associated genes important in neuronal function. Interestingly, using GeneMANIA and Cytoscape we also show that the ASD‐risk genes identified in both COX‐1−/−and COX‐2−/− models belong to protein‐interaction networks important for brain development despite of different cellular localization of these enzymes. Lastly, we identified eight genes that belong to the Wnt signalling pathways exclusively in the COX‐2−/− mice at E16. The level of PKA‐phosphorylated β‐catenin (S552), a major activator of the Wnt pathway, was increased in this model, suggesting crosstalk between the COX‐2‐PGE2 and Wnt pathways during early brain development. Overall, these results provide further molecular insight into the contribution of the COX‐PGE2 pathways to ASD and demonstrate that COX‐1−/− and COX‐2−/− animals might be suitable new model systems for studying the disorders.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.002 | 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 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".