Abstract 185: Muscle Enriched A-Type Lamin Interacting Protein (MLIP) mediates growth and function of the adult heart
Bibliographic record
Abstract
The newly discovered Muscle-enriched A-type lamin interacting protein (MLIP) is abundantly expressed in the heart. Its biological function remains elusive but it may be of high relevance for cardiac function as it has no paralogous homologue suggesting no functional redundancy. To elucidate MLIP’s function, we generated both hemizygous MLIP and homozygous MLIP null mice. At 8 weeks of age, they both develop dilated cardiomyopathy characterized by enlarged hearts (heart to body weights MLIP+/+ 5.62mg/g vs MLIP+/- 10.73mg/g & MLIP -/- 11.03mg/g) that are functionally dilated (LVDD : +/+ 2.89mm; +/- 3.93mm; -/- 4.11mm) with reduced function (LVFS : +/+ 47%; +/- 31%; -/- 29%). Histological analysis shows no overt abnormalities for both MLIP+/- and MLIP-/- hearts. Preliminary data indicate a preserved cardiomyocyte size in MLIP+/- and MLIP-/- mice, suggesting that the increase in heart size might be due to hyperplasia rather than cellular hypertrophy. Moreover, cardiac gene expression of 12 week-old MLIP+/- and MLIP-/- mice reveals an involvement in pathways associated with cell cycle control and growth. Specifically both gene expression and western analysis demonstrated that the mTORC1 pathway, that promotes protein synthesis and cell growth in response to mitogenic signal, was dysregulated in MLIP null mice. To further characterize these growth pathways the MLIP +/+ MLIP +/- and MLIP -/- mice (n = 3-5/group) were treated with 20 μg/g/day of isoproterenol through an abdominally implanted Alzet micropump for 3 weeks to induce heart failure. All mice went under echocardiographic analysis and were characterized by western, gene expression and histological analysis. Our preliminary data reveal that MLIP null mice are resistant to isoproterenol-induced heart failure as their hearts showed no increase in mass, unlike the significant (p<0.01) increase in heart mass observed in both the control mice (31%) or the MLIP hemizygous mice (19%). No cardiac remodeling was observed in either the MLIP hemizygous or null mice in response to the isoproterenol treatment. In conclusion, MLIP is a newly discovered protein that impacts key pathways involved in cardiac growth and function of an adult heart failure model.
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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 | 0.001 |
| 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".