Gait Abnormalities and Aberrant D2 Receptor Expression and Signaling in a Mouse Model of the Human Pathogenic Mutation <i> DRD2 <sup>I212F</sup> </i>
Bibliographic record
Abstract
Abstract A dopamine D2 receptor mutation was recently identified in a family with a novel hyperkinetic movement disorder (Mov Disord 36 : 729-739, 2021). That allelic variant D2-I 212 F is a constitutively active and G protein-biased receptor. We now describe mice engineered to carry the D2-I 212 F variant, Drd2 I212F . The mice exhibited gait abnormalities resembling those in other mouse models of chorea and/or dystonia, and had decreased striatal D2 receptor expression. Electrically evoked IPSCs in midbrain dopamine neurons and striatum from Drd2 I212F mice exhibited slow onset and decay compared to wild type mice. In the presence of dopamine, current decay initiated by photolytic release of sulpiride from CyHQ-sulpiride was slower in midbrain slices from Drd2 I212F mice than Drd2 +/+ mice. Furthermore, in contrast to wild type mice in which dopamine is more potent at neurons in the nucleus accumbens than in the dorsal striatum, reflecting activation of Gα o vs. Gα i1 , dopamine had similar potencies in those two brain regions of Drd2 I212F mice. Repeated cocaine treatment, which decreases dopamine potency in the nucleus accumbens of wild type mice, had no effect on dopamine potency in Drd2 I212F mice. The results demonstrate the utility of this mouse model for investigating the role of pathogenic DRD2 variants in early-onset hyperkinetic movement 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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) | 0.003 | 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".