Year: 2016
Type: article
Abstract: Congenital heart disease is the most common type of birth defect, affecting ~2% of the population.Malformations involving the cardiac outflow tract and semilunar valves account for >50% of these cases predominantly because of bicuspid aortic valve (BAV), which has an estimated prevalence of 1% in the population.Mutations in NOTCH1 have been previously reported to be a cause of BAV and BAVassociated aortopathy in non-syndromic autosomal-dominant human pedigrees.Ascending aortic aneurysms (AscAA) are associated with BAV and are a significant cause of morbidity and mortality in humans.While the exact etiology is unknown, hemodynamic and genetic factors play important roles.Here, we have sought to determine the roles for Notch1 in aortic valve disease and AscAA, and we have identified distinct cell lineages in which loss of Notch1 contributes to BAV and AscAA.We previously described a highly penetrant mouse model of aortic valve disease in Notch1-haploinsufficient adult mice backcrossed into a Nos3-null background (Notch1 +/-; Nos3 -/-mice).Notch1 +/-;Nos3 -/-mice have BAV with thickened valve cusps and associated stenosis and regurgitation.In chapter 2, we describe the congenital cardiac abnormalities in Notch1 +/-; Nos3 -/-embryos that lead to ~65% lethality by postnatal day 10.Although expected Mendelian ratios learn in a way that worked best for me.He permitted me to work independently, let me fail, and learn from my mistakes.I don't know if I would have been successful in a lab that did not afford me that freedom.I was also lucky to have a second mentor in Dr. Brenda Lilly.She always made time for discussion and kept me on my toes by challenging my ideas and scientific knowledge.She taught me to always think about what's next, which is a valuable lesson for any scientist.It was a pleasure to work in the Center for Cardiovascular Research at Nationwide Children's Hospital.The faculty, with their open door policy, really made me feel comfortable seeking advice.The Garg lab members were always encouraging and helpful, creating a great environment for learning.Specifically, I want to thank the early members of the lab -Dr.
Author: Sara N. Koenig
Institution: The Ohio State University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2888451724