Published Online
on November 12, 2007

A more recent version of this article appeared on November 27, 2007

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Submitted on February 21, 2007
Accepted on August 31, 2007

Abnormal Conduction and Morphology in the Atrioventricular Node of Mice With Atrioventricular Canal–Targeted Deletion of Alk3/Bmpr1a Receptor

Dina Myers Stroud PhD, Vinciane Gaussin PhD, John B.E. Burch PhD, Cindy Yu BS, Yuji Mishina PhD, Michael D. Schneider MD, Glenn I. Fishman MD, and Gregory E. Morley PhD^*

From the Leon H. Charney Division of Cardiology (D.M.S., C.Y., G.I.F., G.E.M.), New York University School of Medicine, New York, NY; Department of Cell Biology and Molecular Medicine (V.G.), Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark; Cell and Developmental Biology Program (J.B.E.B.), Fox Chase Cancer Center, Philadelphia, Pa; National Institute of Environmental Health Sciences (Y.M.), Mason, Ohio; and Center for Cardiovascular Development (M.D.S.), Baylor College of Medicine, Houston, Tex.

^* To whom correspondence should be addressed. E-mail: Gregory.Morley{at}nyumc.org.

Background—The atrioventricular (AV) node is essential for the sequential excitation and optimized contraction of the adult multichambered heart; however, relatively little is known about its formation from the embryonic AV canal. A recent study demonstrated that signaling by Alk3, the type 1a receptor for bone morphogenetic proteins, in the myocardium of the AV canal was required for the development of both the AV valves and annulus fibrosus. To test the hypothesis that bone morphogenetic protein signaling also plays a role in AV node formation, we investigated conduction system function and AV node morphology in adult mice with conditional deletion of Alk3 in the AV canal.

Methods and Results—High-resolution optical mapping with correlative histological analysis of 28 mutant hearts revealed 4 basic phenotypic classes based on electrical activation patterns and volume-conducted ECGs. The frequency of AV node conduction and morphological abnormalities increased from no detectable anomalies (class I) to severe defects (class IV), which included the presence of bypass tracts, abnormal ventricular activation patterns, fibrosis of the AV node, and twin AV nodes.

Conclusions—The present findings demonstrate that bone morphogenetic protein signaling is required in the myocardium of the AV canal for proper AV junction development, including the AV node.

Key words: atrioventricular node • genes • electrophysiology

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