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Mouse models of patent ductus arteriosus (PDA) and their relevance for human PDA |
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| Authors: | Michael T. Yarboro Srirupa H. Gopal Rachel L. Su Thomas M. Morgan Jeff Reese |
| Affiliation: | 1. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA Contribution: Conceptualization (equal), Data curation (equal), Funding acquisition (equal), Investigation (equal), Methodology (equal), Validation (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Pediatrics, Erlanger Health System, Chattanooga, Tennessee, USA Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal);3. Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA Contribution: Data curation (equal), Methodology (equal), Writing - original draft (equal);4. Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA Contribution: Data curation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal);5. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA |
| Abstract: | The ductus arteriosus (DA) is a unique fetal vascular shunt, which allows blood to bypass the developing lungs in utero. After birth, changes in complex signaling pathways lead to constriction and permanent closure of the DA. The persistent patency of the DA (PDA) is a common disorder in preterm infants, yet the underlying causes of PDA are not fully defined. Although limits on the availability of human DA tissues prevent comprehensive studies on the mechanisms of DA function, mouse models have been developed that reveal critical pathways in DA regulation. Over 20 different transgenic models of PDA in mice have been described, with implications for human DA biology. Similarly, we enumerate 224 human single-gene syndromes that are associated with PDA, including a small subset that consistently feature PDA as a prominent phenotype. Comparison and functional analyses of these genes provide insight into DA development and identify key regulatory pathways that may serve as potential therapeutic targets for the management of PDA. |
| Keywords: | congenital heart defect ductus arteriosus neonatal circulatory transition vascular biology |