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Conditional Inactivation of the E-Cadherin Gene in Thyroid Follicular Cells Affects Gland Development but Does Not Impair Junction Formation

Istituto di Endocrinologia e Oncologia Sperimentale-Consiglio Nazionale delle Ricerche (G.C., M.Z.), 80131 Napoli, Italy; MicroSCoBiO Research Center and IFOM Center of Cell Oncology and Ultrastructure, Department of Experimental Medicine, University of Genova (P.R., C.T.), 16145 Genova, Italy; Dipartimento di Biologia e Patologia Cellulare e Molecolare, University Federico II (B.D., D.T., M.D.F., L.N.), 80131 Napoli, Italy; BIOGEM: Biotechnology and Molecular Genetics in Southern Italy (A.A., E.A., R.D.L.), 83031 Ariano Irpino, Avellino, Italy; Department of Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum (T.W., G.S.), D-69120 Heidelberg, Germany; Max-Planck Institute (O.B., R.K.), 80804 Freiburg, Germany; and Stazione Zoologica A. Dohrn (D.S.), 80121 Napoli, Italy

Address all correspondence and requests for reprints to: Professor Lucio Nitsch, Dipartimento di Biologia e Patologia Cellulare e Molecolare, University Federico II, Via S. Pansini 5, 80131 Napoli, Italy. E-mail: nitsch{at}unina.it.

We have conditionally inactivated the E-cadherin gene in the thyroid follicular cells of mouse embryo to unravel its role in thyroid development. We used the Cre-loxP system in which the Cre-recombinase was expressed under the control of the tissue-specific thyroglobulin promoter that becomes active at embryonic d 15. At postnatal d 7, thyroid follicle lumens in the knockout mice were about 30% smaller with respect to control mice and had an irregular shape. E-cadherin was almost completely absent in thyrocytes, ß-catenin was significantly reduced, whereas no change in -catenin was detected. -Catenin was also reduced on the cell plasma membrane. Despite the dramatic loss of E-cadherin and ß-catenin, cell-cell junctions were not affected, the distribution of tight junction proteins was unaltered, and no increase of thyroglobulin circulating in the blood was observed. In addition, we found that other members of the cadherin family, the R-cadherin and the Ksp-cadherin, were expressed in thyrocytes and that their membrane distribution was not altered in the E-cadherin conditional knockout mouse. Our results indicate that E-cadherin has a role in the development of the thyroid gland and in the expression of ß-catenin, but it is not essential for the maintenance of follicular cell adhesion.