Insertional mutagenesis in PLN <sup>R9C</sup> transgenic mouse: a case report and a review of the literature on cardiac-specific transgenic expression
Bibliographic record
Abstract
Abstract A mouse line with heterozygous transgenic expression of phospholamban carrying a substitution of cysteine for arginine 9 (PLN R9C ) under the control of α-myosin heavy chain (αMHC) promoter features dilated cardiomyopathy, heart failure and premature death. In this line the transgenic array of 13 PLN R9C expression cassettes, arranged in a head-to-tail tandem orientation, has integrated into the homologous genomic site, the bi-directional promoter of the αMHC (Myh6) gene and the gene for the regulatory non-coding RNA Myheart (Mhrt), both of which are involved in the execution of the α/β MHC switch during cardiac development and pathology. PLN R9C overexpression is evident at the age of 1 month but declines dramatically along with a less pronounced concomitant decline of the resident PLN expression, until the animals die. Expression of the non-coding RNA Mhrt in PLN R9C mice also exhibits a profound deregulation, despite the presence of the second, intact allele. Hence the mouse strain does not faithfully model a human PLN R9C heterozygote, wherein both the mutant and the wildtype PLN alleles have, in all likelihood, the same temporal expression profile. The intricate regulatory circuit of the α/β MHC switch, involving the non-coding RNA Mhrt, was described in detail only recently, and since publications about αMHC-driven transgenes rarely contain the definition of the transgene integration site or temporal expression profile, it is suggested that some of the pathological phenomena attributed to expression of αMHC-driven transgenes may have an alternative explanation.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.004 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".