Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice
Bibliographic record
Abstract
BACKGROUND: Fragile X syndrome is caused by the loss of the Fmr1 gene expression. Deletion of Fmr1 in various neuronal and non-neuronal subpopulations in the brain of mice leads to cell-type-specific effects. Microglia, immune cells critical for the refinement of neuronal circuits during brain development, have been implicated in various neurodevelopmental disorders, including fragile X syndrome. However, it is unknown whether reduced Fmr1 expression in microglia leads to molecular and behavioral phenotypes. METHODS: We downregulated Fmr1 in microglia during early and late postnatal development and studied the effect on microglial morphology and distinct behaviours. RESULTS: Female, but not male, adult mice with downregulation of Fmr1 in microglia during early development exhibited reactive microglia and behavioral phenotypes, including enhanced self-grooming and alterations in social interaction. Downregulation of Fmr1 in microglia during late development induced a milder phenotype, characterized by impaired preference for social novelty without affecting microglia morphology. CONCLUSIONS: The downregulation of Fmr1 and its encoded protein FMRP in microglia contributes to behavioural phenotypes in a sex-specific manner.
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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".