| Abstrakt: |
Previous studies have shown that the Sonic hedgehog(Shh)/Gli signaling pathway is crucial for murine lung development. Both Shh and Gli2 null mice suffer a variety of deficiencies including lobar malformation and hypoplasia of the lung. In the Gli2 null lung, previous studies have shown a 40% reduction in cellular proliferation of the lung mesenchyme. In an attempt to rescue the phenotype of the Gli2 null lung we developed a transgenic mouse which expresses Gli2 in the lung mesenchyme (approximating its native area of expression) using the human versican promoter (hVER). These mice were then crossed for several generations with Gli2 null mice to obtain a mouse expressing the hVER-Gli2 construct in a Gli2 null background. However, these "rescue" mice die at birth due to respiratory insufficiency. On histological examination, it was shown that the hVER-Gli2 construct failed to rescue the left lung isomerism and lung hypoplasia. Closer examination using quantitative real-time PCR .revealed an increase in several growth factors (Fgf1, Fgf7, Fgf9,and Fgf10), cell cycle regulators (Cyclin D1, Cyclin D2, and Cyclin E1), as well as several other related signaling molecules (Tbx4, Tbx5, Mycn, and Cdc25b) the exact opposite of which is seen in the Gli2 null lung. Initial examination of effects on whole lung proliferation using immunohistochemistry to Ki67 failed to show any gross changes in lung growth. [ABSTRACT FROM AUTHOR] |
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