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Zusammenfassung:
Proper regulation of E-cadherin expression is important during early embryonic development, but little is known about the regulatory elements which govern E-cadherin transcriptional activity in vivo. We report the developmentally regulated expression of different E-cadherin-lacZ reporter constructs with sequences of the E-cadherin gene between -6 and +16 kb. Expression of these transgenes were compared with endogenous E-cadherin expression and β-galactosidase expression of a generated E-cadherin knock-in mouse strain. Our results indicate that a promoter fragment from -1.5 to +0.1 kb is insufficient to drive E-cadherin expression in vivo. Moreover, it lacks cis-active elements that activate transcription. We identified brain-specific regulatory elements between -6 and -1.5 kb, endoderm-specific elements between +0.1 and +11 kb and sequences that generally enhance transcription between +11 and +16kb. However, variability of the expression patterns in transgenic lines and lack of expression in ectoderm was observed. Although proper downregulation of the transgene occurs during formation of mesoderm and activation endoderm, the analyzed sequences are insufficient to confer to complete E-cadherin expression. In contrast to that expression of E-cadherin-lacZ knock-in mice reflect the entire and endogeneous E-cadherin gene activity.
