Abstract P1181: Targeted Loss Of Sarcolemmal Membrane Associated Protein Isoform 3 (slmap3) In Cardiac Progenitors Stunts The Embryonic Growth Of Myocardium
Bibliographic record
Abstract
Sarcolemmal membrane associated proteins (SLMAPs) belong to the superfamily of tail anchored membrane proteins known to regulate variety of functions including vesicle transport. SLMAP3 is the largest isoform which is ubiquitously expressed and has been linked to Brugada syndrome and sodium channel activity. SLMAP3 is expressed during cardiogenesis, and we examined its role by nullifying its expression in mouse cardiac progenitors using the Nkx2.5-cre-lox system. Hearts from SLMAP3-knockout (KO) mouse embryos at different stages of cardiogenesis, e9.5, e12.5 and e16.5, were smaller (p<0.05) than wildtype (Wt) littermates. Histological analysis of heart wall measurements from the left ventricles revealed thinner walls in SLMAP3-KO from e9.5 (-25.16%, p<0.05), e12.5 (-29.36%, p<0.05) and e16.5 (-40.27%, p<0.05) compared to Wt although normal chamber formations was observed at these developmental stages. To evaluate the potential reasons for the early difference in cardiac growth, we examined myocardial cell numbers and size with markers of proliferation and hypertrophy. Immunofluorescent analysis of e12.5 hearts with proliferative markers (pH3, Ki67) was not significantly (-5%, p>0.05) altered in KO hearts while cardiomyocyte size differences assessed by immunofluorescence with anti-Troponin C, revealed that KO cardiomyocytes were significantly (-19.4%, p<0.05) smaller than Wt. However, the phospho-to total ratios of AKT1(1.45%, p>0.05) and MTOR1(-12%, p>0.05) were not significantly altered in KO hearts when compared to Wt. SLMAP3 has been implicated in Hippo signaling via the STRIPAK (striatin interacting phosphatase and kinase) complex to impact YAP/TAZ and cell growth. Western blot analysis of e12.5 Wt and KO hearts showed no change in phosphorylation of MST1/2(-6.64%, p>0.05) or YAP-Ser 127(-8.84%, p>0.05) ruling out involvement of Hippo signaling. Interestingly, the expression of the other SLMAP isoforms, SLMAP1 and SLMAP2 remained unaffected during cardiac development in SLMAP3 KO hearts. Thus, SLMAP expression is critical for normal development since the loss of SLMAP3 isoform leads to stunted growth of the embryonic heart. Supported by CIHR.
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| 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".