Generation of mice with conditionally activated transforming growth factor beta signaling through the TbetaRI/ALK5 receptor.
Fiche publication
Date publication
décembre 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BERTHET Cyril
Tous les auteurs :
Bartholin L, Cyprian FS, Vincent D, Garcia CN, Martel S, Horvat B, Berthet C, Goddard-Leon S, Treilleux I, Rimokh R, Marie JC
Lien Pubmed
Résumé
We generated a transgenic mouse strain (LSL-TbetaRI(CA)) containing a latent constitutively active TGFbeta type I receptor (TbetaRI/ALK5) by using a knock-in strategy into the X chromosome-linked hypoxanthine phosphoribosyl-transferase (Hprt) locus. Transgene expression, under the control of the ubiquitous CAG (human cytomegalovirus enhancer and chicken beta-actin) promoter, is repressed by a floxed transcriptional "Stop" (LSL, Lox-Stop-Lox). In the presence of cre-recombinase, the "Stop" is excised to allow TbetaRI(CA) transgene expression. We showed that restricted expression of TbetaRI(CA) in T lymphocytes efficiently activates TGFbeta signaling and rescues the T-cell autoimmune disorders of TGFbetaRII conditional knockouts. Unexpectedly, our study reveals that TGFbeta signaling upregulation controls T-cell activation but does not impair their development or their peripheral homeostasis. In addition to the information provided on TGFbeta effects on T-cell biology, LSL-TbetaRI(CA) mouse constitutes an attractive tool to address the effect of TGFbeta signaling upregulation in any cell type expressing the cre-recombinase.
Référence
Genesis. 2008 Dec;46(12):724-31.