Published ahead of print on August 6, 2003, doi:10.1165/rcmb.2002-0266OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 3, March 2004, 360-366 A more recent version of this article appeared on March 1, 2004
Submitted on November 22, 2002 Fetal Lungs of Tenascin-C-Deficient Mice Grow Well, but Branch Poorly in Organ CultureMatthias Roth-Kleiner1,1 Institute of Anatomy, University of Bern, Bern, Switzerland; Division of Neonatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 2 Max-Planck-Institute of Biochemistry, Martinsried, Germany, 3 Institute of Anatomy, University of Bern, Bern, Switzerland * To whom correspondence should be addressed. E-mail: schittny{at}ana.unibe.ch.
Tenascin-C (TNC) is a multi-domain extracellular matrix protein, which 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 three days. In lung explants of homozygote TNC deficient embryos (E12.5) the number of future airway branches was reduced by 36% as compared to wildtype. 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 morphological investigation at postnatal day P2, where the airspaces of TNC deficient lungs appeared larger than in wildtypes. Taken together, our result represents 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. Since TNC is predominately 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.
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