Epithelial transport and barrier function in occludin-deficient mice

Background and Aims: This study aimed at functional characterization of the tight junction protein occludin using the occludin-deficient mouse model. Methods: Epithelial transport and barrier functions were characterized in Ussing chambers, Impedance analysis revealed the ionic permeability of the epithelium (R-c, epithelial resistance). Conductance scanning differentiated transcellular (G(c)) and tight junctional conductance (G(tJ)). The pH-stat technique quantified gastric acid secretion. Results: In occludin(+/+) mice, R-c was 23 +/- 5 Omega cm(2) in jejunum, 66 +/- 5 Omega cm(2) in distal colon and 33 +/- 6 Omega cm(2) in gastric corpus and was not altered in heterozygotic occludin+/- or homozygotic occludin-/- mice. Additionally, [H-3]mannitol fluxes were unaltered. In the control colon, G(c) and G(tj) were 7.6 +/- 1.0 and 0.3 +/- 0.1 mS/cm(2) and not different in occludin deficiency. Epithelial resistance after mechanical perturbation or EGTA exposition (low calcium switch) was not more affected in occhidin-/- mice than in control. Barrier function was measured in the urinary bladder, a tight epithelium, and in the stomach. Control R-t was 5.9 +/- 0.8 k Omega cm(2) in Urinary bladder and 33 +/- 6 Omega cm(2) in stomach and not altered in occludin-/- mice. In gastric corpus mucosa, the glandular structure exhibited a complete loss of parietal cells and mucus cell hyperplasia, as a result of which acid secretion was virtually abolished in occludin-/- mice. Conclusion: Epithelial barrier characterization in occludin-deficiency points against an essential barrier function of occludin within the tight junction strands or to a substitutional redundancy of single tight junction molecules like occludin. A dramatic change in gastric morphology and secretory function indicates that occludin is involved in gastric epithelial differentiation. (C) 2005 Elsevier B.V. All rights reserved.