Defective epidermal barrier in neonatal mice lacking the C-terminal region of connexin43

Mol Biol Cell. 2004 Oct;15(10):4597-608. doi: 10.1091/mbc.e04-04-0324. Epub 2004 Jul 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers
  • Cell Differentiation
  • Connexin 43 / chemistry
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Electrocardiography
  • Epidermis / abnormalities*
  • Epidermis / chemistry
  • Epidermis / metabolism*
  • Female
  • Filaggrin Proteins
  • Gap Junctions / metabolism
  • Heart / physiology
  • Heart Defects, Congenital
  • Intermediate Filament Proteins / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardium / cytology
  • Myocardium / metabolism
  • Ovary / abnormalities
  • Ovary / metabolism
  • Phosphoproteins / metabolism
  • Survival Rate
  • Zonula Occludens-1 Protein

Substances

  • Biomarkers
  • Connexin 43
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Membrane Proteins
  • Phosphoproteins
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein