Abstract 8396: A Novel Lamin Interactor (MLIP) is Critical for Cardiac Development and its Potential Role in DCM
Bibliographic record
Abstract
A-type lamins have been implicated in the maintenance of cellular commitment and differentiation. Mutations in the LMNA gene are associated with cardiac conduction disease and dilated cardiomyopathy (DCM) in humans. The molecular mechanisms that relate mutations in LMNA with different human diseases are poorly understood and its interactions become of prominence. Using protein:protein interaction assays against Lamin A/C we discovered a novel muscle enriched lamin interacting protein (MLIP) from human heart. MLIP (C6orf142 & 2310046A06rik) is a unique single copy gene that is an innovation of amniotes (reptiles, birds and mammals). The MLIP gene encodes alternatively spliced protein variants (23 to 57kDa) that possess several novel structural motifs not found in other proteins. Like Lamin A/C, MLIP is ubiquitously expressed with tissue specific isoforms found most abundantly in heart, skeletal and smooth muscle. MLIP interacts directly and co-localizes with Lamin A and C in the nuclear envelope. Down-regulation of Lamin A/C expression by shRNA results in the up-regulation and mis-localization of MLIP. In the developing mouse heart MLIP is differentially expressed from E9 to adulthood. Conditional MLIP homozygous null mice die in utero , while hemizygous MLIP null mice develop DCM by 8 weeks of age (Table 1). Ongoing longitudinal studies combining echo with microSPECT-CT will further define the DCM phenotype. In addition to interacting with Lamin, MLIP also binds to genomic DNA within close proximity of genes encoding transcription factors (including Foxc1/c2, Foxa2, Gata4, Mef2c, Pitx2, Rxra and Tbx2) as determined by chromatin immmunoprecipitation and gel mobility shift assays. In conclusion, MLIP is a newly discovered lamin interacting protein that may serve as a tanscriptional regulator that impact genes involved in cardiac development and provides a new direction to study.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.004 |
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".