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The Nkx2.5 mutation affects impulse conduction of developing heart
Author(s) -
Olejnickova Veronika,
Hamor Peter,
Kvasilova Alena,
Sedmera David
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.585.13
Subject(s) - embryonic heart , heart development , immunohistochemistry , homeobox , anatomy , christian ministry , embryonic stem cell , medicine , impulse (physics) , cardiology , optical mapping , biology , gene expression , gene , quantum mechanics , biochemistry , philosophy , theology , physics
The process of ventricular trabeculation is a crucial step of embryonic heart formation. Trabeculae provide higher contractile force and preserve diffusion distance fitting nutrition range. Their role as a shortcut for electric impulse propagation has been also postulated. The homeobox gene Nkx2.5 is required for the proper heart development with ED 9–10 embryonic mortality in its absence. The present work tested in a mouse model of Nkx2.5 deletion using the GFP knock‐in how the ventricular impulse conduction is affected in trabecular absence. Freshly isolated WT, Nkx2.5 −/− and Nkx2.5 +/− mouse hearts were stained with di‐4‐ANEPPS and analysed using optical mapping. Ventricular chamber differentiation into trabeculae was assessed by whole mount confocal microscopy followed by 3D reconstruction and connexin40 immunohistochemistry detection. The Nkx2.5 −/− embryos showed serious grows retardation with severe heart dysmorphogenesis and very slow conduction reminiscent of the primary heart tube myocardium. There was no expression of connexin40 in the myocardium detected by immunohistochemistry. The Nkx2.5 +/− showed similar heart formation and impulse conduction as wild type controls. We conclude that Nkx2.5 is essential for chamber myocardium differentiation through trabeculation and its complete absence severely affects impulse conduction through the developing mouse heart. Support or Funding Information Supported by GACR 13‐12412S and Ministry of Education PRVOUK P35/LF/5.