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Title: ALK3 deletion targeted to the atrioventricular canal results in defects compatible with Ebstein's anomaly
Authors: Gaussin, V ×
Morley, GE
Cox, L
Hong, C
Depré, C
Myers, D
Tian, YM
Emile, L
Mishina, Y
Behringer, RR
Hanks, MC
Zwijsen, An
Huylebroeck, D
Fishman, GI
Schneider, MD
Burch, JB #
Issue Date: 26-Oct-2004
Host Document: Circulation vol:110 issue:117 pages:59
Conference: Scientific Meeting of the American-Heart-Association edition:77 location:New Orleans date:07-10 Nov 2004
Article number: 272
Abstract: Endocardial cushions are precursors of mature atrioventricular (AV) valves. Their formation is induced by signaling molecules originating from the AV myocardium, including bone morphogenetic proteins (BMPs). Here, we hypothesized that BMP signaling plays an important role in the AV myocardium during the maturation of AV valves from the cushions. To test our hypothesis, we used a unique Cre/lox system to target the deletion of a floxed Alk3 allele, the type IA receptor for BMPs, to cardiac myocytes of the AV canal (AVC). Lineage analysis indicated that cardiac myocytes of the AVC contributed to the tricuspid mural and posterior leaflets, the mitral septal leaflet, and the atrial border of the annulus fibrosus. When Alk3 was deleted in these cells, defects were seen in the same leaflets, ie, the tricuspid mural leaflet and mitral septal leaflet were longer, the tricuspid posterior leaflet was displaced and adherent to the ventricular wall, and the annulus fibrosus was disrupted resulting in ventricular preexcitation. The defects seen in mice with AVC-targeted deletion of Alk3 provide strong support for a role of Alk3 in human congenital heart diseases, such as Ebstein’s anomaly. In conclusion, our mouse model demonstrated critical roles for Alk3 signaling in the AV myocardium during the development of AV valves and the annulus fibrosus.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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