Epithelial transport and barrier function in occludin-deficient mice |
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Authors: | JD Schulzke AH Gitter J Mankertz U Seidler M Saitou M Fromm |
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Institution: | a Department of Gastroenterology, Campus Benjamin Franklin, Charité - Universitary Medicine Berlin, Germany b Department of Clinical Physiology, Campus Benjamin Franklin, Charité - Universitary Medicine Berlin, Germany c Department of Medical Engineering, Jena University of Applied Sciences, Carl-Zeiss-Promenade 2, Jena, Germany d Med. Klinik, Medizinische Hochschule Hannover, Germany e Department of Cell Biology, Kyoto University Faculty of Medicine, Japan |
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Abstract: | Background and AimsThis study aimed at functional characterization of the tight junction protein occludin using the occludin-deficient mouse model.MethodsEpithelial transport and barrier functions were characterized in Ussing chambers. Impedance analysis revealed the ionic permeability of the epithelium (Re, epithelial resistance). Conductance scanning differentiated transcellular (Gc) and tight junctional conductance (Gtj). The pH-stat technique quantified gastric acid secretion.ResultsIn occludin+/+ mice, Re was 23±5 Ω cm2 in jejunum, 66±5 Ω cm2 in distal colon and 33±6 Ω cm2 in gastric corpus and was not altered in heterozygotic occludin+/− or homozygotic occludin−/− mice. Additionally, 3H]mannitol fluxes were unaltered. In the control colon, Gc and Gtj were 7.6±1.0 and 0.3±0.1 mS/cm2 and not different in occludin deficiency. Epithelial resistance after mechanical perturbation or EGTA exposition (low calcium switch) was not more affected in occludin−/− mice than in control. Barrier function was measured in the urinary bladder, a tight epithelium, and in the stomach. Control Rt was 5.8±0.8 kΩ cm2 in urinary bladder and 33±6 Ω cm2 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.ConclusionEpithelial 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. |
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Keywords: | AC alternating current ISC short-circuit current Rt total tissue resistance Re resistance of the epithelial layer Rsub resistance of the subepithelial tissues Gt total tissue conductivity Gse conductivity of the surface epithelium Gcry conductivity of the crypts Gc conductivity of the transcellular pathway Gtj conductivity of the paracellular (i e tight junctional) pathway NS not significant |
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