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MBC in Press, published online ahead of print July 28, 2004
Mol. Biol. Cell 10.1091/mbc.E04-04-0324

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Submitted on April 20, 2004
Revised on July 9, 2004
Accepted on July 13, 2004

Defective Epidermal Barrier in Neonatal Mice Lacking the C-Terminal Region of Connexin43

Karen Maass*, Alexander Ghanem{dagger}, Jung-Sun Kim{ddagger}, Manuela Saathoff{sect}, Stephanie Urschel*, Gregor Kirfel{sect}, Ruth Grümmer||, Markus Kretz*, Thorsten Lewalter{dagger}, Klaus Tiemann{dagger}, Elke Winterhager||, Volker Herzog{sect}, and Klaus Willecke*¶

*Institut für Genetik, Universität Bonn, D-53117 Bonn, Germany; {dagger}Medizinische Klinik II, Kardiologie und Pneumologie, Universität Bonn, D-53105 Bonn, Germany; {ddagger}University of Ulsan, College of Medicine, Seoul, Republic of Korea; {sect}Institut für Zellbiologie, Universität Bonn, D-53121 Bonn, Germany; ||Medizinische Fakultät der Universität Duisburg-Essen, D-45122 Essen, Germany

Monitoring Editor: Daniel Goodenough

More than 97% of mice in which the C-terminal region of connexin43 (Cx43) was removed (designated as Cx43K258stop) die shortly after birth due to a defect of the epidermal barrier. The abnormal expression of Cx43K258stop protein in the uppermost layers of the epidermis appears to perturb terminal differentiation of keratinocytes. In contrast to Cx43 deficient mice, neonatal Cx43K258stop hearts show no lethal obstruction of the right ventricular outflow tract, but signs of dilatation. Electrocardiographies of neonatal hearts reveal repolarization abnormalities in 20% of homozygous Cx43K258stop animals. The very rare adult Cx43K258stop mice show a compensation of the epidermal barrier defect but persisting impairment of cardiac function in echocardiography. Female Cx43K258stop mice are infertile due to impaired folliculogenesis. Our results indicate that the C-terminally truncated Cx43K258stop mice lack essential functions of Cx43, although the truncated Cx43 protein can form open gap junctional channels.

Corresponding author. E-mail: genetik{at}uni-bonn.de




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