A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment
Bibliographic record
Abstract
Human Menkes disease is a lethal neurodegenerative disorder of copper metabolism that is caused by mutations in the ATP7A copper-transporting gene. In the present study, we attempted to construct a Drosophila model of Menkes disease by RNA interference (RNAi)-induced silencing of DmATP7, the Drosophila orthologue of mammalian ATP7A, in the digestive tract. Here, we show that a lowered level of DmATP7 mRNA in the digestive tract results in a reduced copper content in the head and the rest of the body of surviving adults, presumably owing to copper entrapment in the gut. Similar to Menkes patients, a majority of flies exhibit an impaired neurological development during metamorphosis and die before eclosion. In addition, we show that survival to the adult stage is highly dependent on the copper content of the food and that overexpression of the copper homeostasis gene, metal-responsive transcription factor-1 (MTF-1), enhances survival to the adulthood stage. Taken together, these results highlight the role of DmATP7-mediated copper uptake in the neurodevelopment of Drosophila melanogaster and provide a framework for the analysis of potential gene interactions influencing Menkes disease.
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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".