title: Loss of Notch2 and Notch3 in vascular smooth muscle causes patent ductus arteriosus.
abstract: The overlapping roles of the predominant Notch receptors in vascular smooth muscle cells, Notch2 and Notch3, have not been clearly defined in vivo. In this study, we use a smooth muscle-specific deletion of Notch2 together with a global Notch3 deletion to produce mice with combinations of mutant and wild-type Notch2/3 alleles in vascular smooth muscle cells. Mice with complete loss of Notch3 and smooth muscle-expressed Notch2 display late embryonic lethality and subcutaneous hemorrhage. Mice without smooth muscle-Notch2 and only one wild-type copy of Notch3 die within one day of birth and present with vascular defects, most notably patent ductus arteriosus (DA) and aortic dilation. These defects were associated with decreased expression of contractile markers in both the DA and aorta. These results demonstrate that Notch2 and Notch3 have overlapping roles in promoting development of vascular smooth muscle cells, and together contribute to functional closure of the DA.
authors.affiliation: Nationwide Children's Hospital, Center for Cardiovascular and Pulmonary Research and the Heart Center, Columbus, Ohio.|Department of Pediatrics, the Ohio State University, Columbus, Ohio.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Baeten
authors.affiliation: Center for Molecular Human Genetics, Nationwide Children's Hospital, Columbus, Ohio.|Division of Anatomy, the Ohio State University, Columbus, Ohio.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Jackson
authors.affiliation: Center for Molecular Human Genetics, Nationwide Children's Hospital, Columbus, Ohio.|Division of Anatomy, the Ohio State University, Columbus, Ohio.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: McHugh
authors.affiliation: Nationwide Children's Hospital, Center for Cardiovascular and Pulmonary Research and the Heart Center, Columbus, Ohio.|Department of Pediatrics, the Ohio State University, Columbus, Ohio.
authors.forename: Brenda
authors.initials: B
authors.lastname: Lilly
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004374:Ductus Arteriosus, Patent / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497765:Notch2 protein, mouse; C499373:Notch3 protein, mouse; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D051880:Receptors, Notch
keywords: Notch signaling; differentiation; smooth muscle development