The immediate upstream sequence of the mouse Ret gene controls tissue-specific expression in transgenic mice

Abstract

The RET gene is tightly regulated at the transcriptional level during embryo development, however in vitro experiments in cultured cells have failed to clarify the molecular mechanism of cell-type specificity of RET promoter activity. Therefore, we have generated transgenic mice in which the LacZ reporter gene is controlled by murine Ret promoter sequences to clarify in an in vivo model how this transcriptional regulation is achieved. We describe here the results of reporter gene expression in mice in which the transgene contained 380- and 1962-bp sequence upstream of the ATG start codon, derived from the mouse Ret promoter region, fused to the β-galactosidase coding sequence. Transgenic mice showed well-defined patterns of β-galactosidase staining obtained with both transgenes, suggesting that they were able per se to direct the reporter gene expression in specific districts, such as cranial ganglia, dorsal root ganglia, the heart and the kidney, partially recapitulating the profile of the endogenous Ret gene. In particular, proper expression in the developing excretory system seemed quite significant when considering that the appropriate regulation was obtained with a very short, 380 bp, fragment of Ret 5′ flanking sequence.