GABA A Receptor Gamma 3 is a New Candidate Gene for Cardiovascular and Behavioral Disorders
Bibliographic record
Abstract
We previously discovered a significant locus on mouse chromosome (chr) 7 that controls elevated heart rate in a genetic cross between C3HeB and SJL mice. Association mapping within the locus revealed three subunits of gamma‐aminobutyric acid (GABA) A receptors. The mouse chr7 locus is syntenic to human chr15q locus and is important for mental disorders as well as heart rate variation. The goal of this study was to further investigate the GABAA receptors as candidate genes in the regulation of the cardiovascular system. First, we evaluated expression profiles of the candidate genes in several organs between C3HeB and SJL strains. There was higher mRNA expression of all three GABAA receptors in mouse brain compared to other organs in both strains. We found that alpha5 (~14‐fold) and gamma3 (~5‐fold) were significantly higher in brains from C3HeB compared to SJL mice. In addition, gamma3 mRNA levels were greater in the C3HeB hearts (~20‐fold). Western blot analyses of brain and heart confirmed higher expression of the gamma3 protein in C3HeB versus SJL mice. We genetically targeted the gamma3 gene by using a knockout first and promoter driven reporter tag strategy. Mice with positive alleles for gamma3 showed persistent beta‐galactosidase staining in the brain at embryonic days E12.5 and E15.5. In summary, GABAA gamma3 receptor is a strong candidate gene for elevated heart rate within the mouse chr7 locus. We developed a new mouse model with conditional potential that will allow us to investigate contribution of GABAA gamma3 receptor in cardiovascular and behavioral 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 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".