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Beckert, V.* ; Rassmann, S.* ; Kayvanjoo, A.H.* ; Klausen, C.* ; Bonaguro, L.* ; Botermann, D.S.* ; Krause, M.* ; Moreth, K. ; Spielmann, N. ; Da Silva-Buttkus, P. ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Händler, K.* ; Ulas, T.* ; Aschenbrenner, A.C.* ; Mass, E.* ; Wachten, D.*

Creld1 regulates myocardial development and function.

J. Mol. Cell. Cardiol. 156, 45-56 (2021)
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CRELD1 (Cysteine-Rich with EGF-Like Domains 1) is a risk gene for non-syndromic atrioventricular septal defects in human patients. In a mouse model, Creld1 has been shown to be essential for heart development, particularly in septum and valve formation. However, due to the embryonic lethality of global Creld1 knockout (KO) mice, its cell type-specific function during peri- and postnatal stages remains unknown. Here, we generated conditional Creld1 KO mice lacking Creld1 either in the endocardium (KOTie2) or the myocardium (KOMyHC). Using a combination of cardiac phenotyping, histology, immunohistochemistry, RNA-sequencing and flow cytometry, we demonstrate that Creld1 function in the endocardium is dispensable for heart development. Lack of myocardial Creld1 causes extracellular matrix remodeling and trabeculation defects by modulation of the Notch1 signaling pathway. Hence, KOMyHC mice die early postnatally due to myocardial hypoplasia. Our results reveal that Creld1 not only controls the formation of septa and valves at an early stage during heart development, but also cardiac maturation and function at a later stage. These findings underline the central role of Creld1 in mammalian heart development and function.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Creld1 ; Ecm ; Heart Development ; Notch ; Trabeculation; Atrioventricular Septal-defects; Congenital Heart-disease; Missense Mutations; Down-syndrome; Activation; Association; Expression; Deletion; Package; Access
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0022-2828
e-ISSN 0022-2828
Journal Journal of Molecular and Cellular Cardiology
Quellenangaben Volume: 156, Issue: , Pages: 45-56 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500600-001
G-500692-001
Grants German Federal Ministry of Education and Research
Daimler and Benz Foundation
Fritz Thyssen foundation
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy
German Center for Diabetes Research (DZD)
DOI 10.1016/j.yjmcc.2021.03.008
WOS ID WOS:000662887500005
Scopus ID 85105285594
PubMed ID 33773996
Erfassungsdatum 2021-05-20
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