title: Inducible gene expression in fetal thymic epithelium: a new BAC transgenic model.
abstract: The thymus is the site of T cell development. Several stromal and hematopoietic cell types are necessary for the proper function of thymic selection and eventually peripheral immunity. Thymic epithelial cells (TECs) are essential for T cell lineage commitment, expansion, and maturation in the thymus. We were interested in developing an in vivo model in which exogenous gene expression could be transiently induced in embryonic TEC (Tet-On system). To this end, we have generated a bacterial artificial chromosome (BAC) transgenic mouse line in which the reverse tetracycline-dependent transactivator (rtTA) is expressed under the control of the Foxn1 promoter, a transcriptional factor indispensable for TEC development. To analyze the expression pattern and efficiency of this novel mouse model, we crossed the Foxn1-rtTA founder with a Tet-Responsive Element (TRE)-LacZ GFP mouse reporter to obtain a double transgenic mouse. In the presence of doxycycline, rtTA can interact with TRE and induce the expression of GFP and LacZ. In this double transgenic mouse, we observed that GFP expression was high, inducible and limited to TEC in fetal thymus. In contrast, in adult thymus, when TEC development and maturation is completed, GFP was barely detectable. Therefore, Foxn1-rtTA represents a new and efficient transgenic mouse model to induce genes of interest specifically in fetal thymic epithelium.
authors.affiliation: Ludwig Center for Cancer Research of University of Lausanne, CH-1066, Epalinges, Switzerland.
authors.forename: Emma
authors.initials: E
authors.lastname: Fiorini
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferrero
authors.forename: Caroline
authors.initials: C
authors.lastname: Poisson
authors.forename: Leonardo
authors.initials: L
authors.lastname: Scarpellino
authors.forename: Sanjiv Andreas
authors.initials: SA
authors.lastname: Luther
authors.forename: H Robson
authors.initials: HR
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D022202:Chromosomes, Artificial, Bacterial; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D013950:Thymus Gland / Q000196:embryology* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein
keywords: BAC; Dox; Foxn1-rtTA; TEC