Published ahead of print on August 6, 2003, doi:10.1165/rcmb.2002-0266OC
American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 360-366, 2004
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2002-0266OC
Fetal Lungs of Tenascin-CDeficient Mice Grow Well, but Branch Poorly in Organ Culture
Matthias Roth-Kleiner,
Emilio Hirsch and
Johannes C. Schittny
Institute of Anatomy, University of Bern, Bern; Division of Neonatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and Max-Planck-Institute of Biochemistry, Martinsried, Germany
Address correspondence to: Johannes C. Schittny, Institute of Anatomy, University of Bern, Buehlstrasse 26, CH-3000 Bern 9, Switzerland. E-mail: schittny{at}ana.unibe.ch
Tenascin-C (TNC) is a multidomain extracellular matrix protein that contributes to organogenesis and tumorgenesis. To elucidate its developmental function in the context of TNC deficiency, lung lobes of TNC null mice were obtained at Embryonic Days E11.5 and E12.5 and cultured for 3 d. In lung explants of homozygote TNC-deficient embryos (E12.5) the number of future airway branches was reduced by 36% as compared with wild-type. In heterozygote explants only half of the reduction (18%) was observed. No significant alteration, neither of the explant growth nor of the pattern of airway branching, was noticed in TNC-null explants. However, the terminal endbuds of the transgenic explants were enlarged. The results are supported by a morphologic investigation at Postnatal Day P2, where the airspaces of TNC-deficient lungs appeared larger than in wild-type lungs. Taken together, our results represent the first developmental phenotype of TNC-null mice. We conclude that TNC takes part in the control of fetal lung branching, and that not only the presence of TNC but also its amount is important. Because TNC is predominantly expressed at the growing tip of the future airways, we hypothesize that TNC promotes the penetration into the surrounding mesenchyme and the branching of the growing airways.
Abbreviations: embryonic, E postnatal, P phosphate-buffered saline, PBS Tenascin-C, TNC transferase-mediated deoxyuridine triphosphate nick end labeling, TUNEL
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