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Am J Physiol Cell Physiol 274: C875-C882, 1998;
0363-6143/98 $5.00
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Vol. 274, Issue 4, C875-C882, April 1998

Bioelectric properties of human cystic fibrosis and non-cystic fibrosis fetal tracheal xenografts in SCID mice

Rabindra Tirouvanziam1, Mama Desternes2, Anouar Saari2, Edith Puchelle3, Bruno Péault1, and Thierry Chinet2

1 Institut d'Embryologie Cellulaire et Moléculaire du Centre National de la Recherche Scientifique-Unité Propre de Recherche 9064, 94736 Nogent sur Marne Cedex; 2 Laboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, Université Paris V René Descartes, 92104 Boulogne Cedex; and 3 Institut National de la Santé et de la Recherche Médicale U. 314, 51092 Reims Cedex, France

We measured the bioelectric properties of 14 cystic fibrosis (CF) and 33 non-CF human fetal tracheal xenografts in severe combined immunodeficiency (SCID) mice. All xenografts exhibited a mature airway-type epithelium irrespective of their gestational age, duration of engraftment, and genotype. The in vivo potential difference and the in vitro baseline short-circuit current (Isc) were significantly higher in non-CF than in CF xenografts. In non-CF xenografts, sequential addition of amiloride, forskolin, and ATP resulted in a 39.4% decrease, a 24.1% increase, and a 43.6% increase in Isc, respectively. In CF xenografts, forskolin had no significant effect on Isc, whereas amiloride- and ATP-induced changes in Isc were proportionally higher than in non-CF xenografts (-60.0 and +68.8%, respectively). These results indicate that the bioelectric properties of non-CF xenografts are similar to those of postnatal airways and that CF xenografts exhibit lower baseline electrogenic activity than non-CF xenografts but similar regulation of ion transport processes to postnatal CF airways. This model of mature human fetal tracheal mucosa may help gain insight into early CF airway pathogenesis.

cystic fibrosis transmembrane conductance regulator; airway epithelium; chloride secretion; sodium absorption; fetal airway development


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