Left ventricular noncompaction (LVNC) causes prominent ventricular trabeculations and reduces cardiac systolic function. The clinical presentation of LVNC ranges from asymptomatic to heart failure. We show that germline mutations in human MIB1 (mindbomb homolog 1), which encodes an E3 ubiquitin ligase that promotes endocytosis of the NOTCH ligands DELTA and JAGGED, cause LVNC in autosomal-dominant pedigrees, with affected individuals showing reduced NOTCH1 activity and reduced expression of target genes. Functional studies in cells and zebrafish embryos and in silico modeling indicate that MIB1 functions as a dimer, which is disrupted by the human mutations. Targeted inactivation of Mib1 in mouse myocardium causes LVNC, a phenotype mimicked by inactivation of myocardial Jagged1 or endocardial Notch1. Myocardial Mib1 mutants show reduced ventricular Notch1 activity, expansion of compact myocardium to proliferative, immature trabeculae and abnormal expression of cardiac development and disease genes. These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction.
Pharmacology, Toxicology and Pharmaceutical Science
3
1%
Other
13
5%
Unknown
79
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 November 2022.
All research outputs
#5,992,878
of 28,578,667 outputs
Outputs from Nature Medicine
#6,621
of 10,374 outputs
Outputs of similar age
#56,118
of 304,508 outputs
Outputs of similar age from Nature Medicine
#62
of 105 outputs
Altmetric has tracked 28,578,667 research outputs across all sources so far. Compared to these this one has done well and is in the 78th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,374 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 108.9. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
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We're also able to compare this research output to 105 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
