000232756 001__ 232756
000232756 005__ 20181203024905.0
000232756 0247_ $$2doi$$a10.1172/jci.insight.91353
000232756 022__ $$a2379-3708
000232756 02470 $$2ISI$$a000414267000002
000232756 037__ $$aARTICLE
000232756 245__ $$aNotch1 haploinsufficiency causes ascending aortic aneurysms in mice
000232756 260__ $$bAmer Soc Clinical Investigation Inc$$c2017$$aAnn Arbor
000232756 269__ $$a2017
000232756 300__ $$a15
000232756 336__ $$aJournal Articles
000232756 520__ $$aAn ascending aortic aneurysm (AscAA) is a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a potentially novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Additionally, Notch1(+/-) mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 is sufficient to cause AscAA. RNA sequencing analysis of the Notch1.129S6(+/-) aortic root demonstrated gene expression changes consistent with AscAA. These findings are the first to our knowledge to demonstrate an SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy.
000232756 700__ $$uNationwide Childrens Hosp, Ctr Cardiovasc Res, Room WB4221, Columbus, OH 43205 USA$$aKoenig, Sara N.
000232756 700__ $$aLahaye, Stephanie
000232756 700__ $$uNationwide Childrens Hosp, Ctr Cardiovasc Res, Room WB4221, Columbus, OH 43205 USA$$aFeller, James D.
000232756 700__ $$uNationwide Childrens Hosp, Ctr Cardiovasc Res, Room WB4221, Columbus, OH 43205 USA$$aRowland, Patrick
000232756 700__ $$uNationwide Childrens Hosp, Heart Ctr, Room WB4221, Columbus, OH 43205 USA$$aHor, Kan N.
000232756 700__ $$uNationwide Childrens Hosp, Ctr Cardiovasc Res, Room WB4221, Columbus, OH 43205 USA$$aTrask, Aaron J.
000232756 700__ $$uOhio State Univ, Dept Physiol & Cell Biol, Columbus, OH 43210 USA$$aJanssen, Paul M. L.
000232756 700__ $$0240231$$g172749$$aRadtke, Freddy
000232756 700__ $$uNationwide Childrens Hosp, Ctr Cardiovasc Res, Room WB4221, Columbus, OH 43205 USA$$aLilly, Brenda
000232756 700__ $$uNationwide Childrens Hosp, Ctr Cardiovasc Res, Room WB4221, Columbus, OH 43205 USA$$aGarg, Vidu
000232756 773__ $$j2$$tJci Insight$$k21$$qe91353
000232756 909C0 $$xU11429$$0252086$$pUPRAD
000232756 909CO $$pSV$$particle$$ooai:infoscience.tind.io:232756
000232756 917Z8 $$x181933
000232756 937__ $$aEPFL-ARTICLE-232756
000232756 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000232756 980__ $$aARTICLE