Defective epidermal barrier in neonatal mice lacking the C-terminal region of connexin43.
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 seems 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.
Maass
Karen
K
Institut für Genetik, Universitat Bonn, D-53117 Bonn, Germany.
Ghanem
Alexander
A
Kim
Jung-Sun
JS
Saathoff
Manuela
M
Urschel
Stephanie
S
Kirfel
Gregor
G
Grümmer
Ruth
R
Kretz
Markus
M
Lewalter
Thorsten
T
Tiemann
Klaus
K
Winterhager
Elke
E
Herzog
Volker
V
Willecke
Klaus
K
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D002454:Cell Differentiation; D018031:Connexin 43 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004562:Electrocardiography; D004817:Epidermis / Q000002:abnormalities* / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D000091344:Filaggrin Proteins; D017629:Gap Junctions / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006330:Heart Defects, Congenital; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010053:Ovary / Q000002:abnormalities / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015996:Survival Rate; D062826:Zonula Occludens-1 Protein
D015415:Biomarkers; D018031:Connexin 43; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein