Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018799 (
heart disease
)
34,133
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The recent recovery of mutations in vesicular trafficking genes causing congenital
heart disease
(CHD) revealed an unexpected role for the endocytic pathway. We now show that mice with a C4232R missense mutation in
Low density lipoprotein receptor
related protein 1 (LRP1) exhibit atrioventricular septal defects with double outlet right ventricle. Lrp1
m/m
mice exhibit shortened outflow tracts (OFT) and dysmorphic hypocellular cushions with reduced proliferation and increased apoptosis. Lrp1
m/m
embryonic fibroblasts show decreased cell motility and focal adhesion turnover associated with retention of mutant LRP1 in endoplasmic reticulum and reduced LRP1 expression. Conditional deletion of Lrp1 in cardiac neural crest cells (CNC) replicates the full CHD phenotype. Cushion explants showed defective cell migration, with gene expression analysis indicating perturbation of Wnt and other signaling pathways. Thus, LRP1 function in CNCs is required for normal OFT development with other cell lineages along the CNC migratory path playing a supporting role.
...
PMID:Mutation of LRP1 in cardiac neural crest cells causes congenital heart defects by perturbing outflow lengthening. 3254 59
