title: 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 beta-galactosidase coding sequence. Transgenic mice showed well-defined patterns of beta-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.
authors.affiliation: Laboratory of Molecular Genetics, Giannina Gaslini Institute, 16147 Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zordan
authors.forename: Sara
authors.initials: S
authors.lastname: Tavella
authors.forename: Antonella
authors.initials: A
authors.lastname: Brizzolara
authors.forename: Roberta
authors.initials: R
authors.lastname: Biticchi
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
authors.forename: Silvio
authors.initials: S
authors.lastname: Garofalo
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Renata
authors.initials: R
authors.lastname: Bocciardi
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000818:Animals; D003391:Cranial Nerves / Q000196:embryology / Q000378:metabolism; D017615:Enteric Nervous System / Q000196:embryology / Q000378:metabolism; D005260:Female; D005318:Fetal Heart / Q000196:embryology / Q000378:metabolism; D005724:Ganglia / Q000196:embryology / Q000378:metabolism; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000196:embryology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse; D001616:beta-Galactosidase