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Generation of Mice with Conditionally Activated Transforming Growth Factor Beta Signaling Through the T beta RI/ALK5 Receptor

  1. Author:
    Bartholin, L.
    Cyprian, F. S.
    Vincent, D.
    Garcia, C. N.
    Martel, S.
    Horvat, B.
    Berthet, C.
    Goddard-Leon, S.
    Treilleux, I.
    Rimokh, R.
    Marie, J. C.

  2. Author Address

    Bartholin, Laurent] Ctr Leon Berard, INSERM, Avenir Grp, U590,IFR62, F-69373 Lyon 08, France. [Bartholin, Laurent, Cyprian, Farhan S.; Vincent, David, Garcia, Celine N.; Horvat, Branka, Rimokh, Ruth, Marie, Julien C.] Univ Lyon 1, F-69365 Lyon, France. [Cyprian, Farhan S.; Garcia, Celine N.; Horvat, Branka, Marie, Julien C.] INSERM, U758, IFR128, F-69008 Lyon, France. [Cyprian, Farhan S.; Garcia, Celine N.; Horvat, Branka, Marie, Julien C.] ENS, Lyon, France. [Berthet, Cyril] NIH, Ctr Canc Res, Frederick, MD USA.
    1. Year: 2008
  2. Journal: Genesis
    1. 46
    2. 12
    3. Pages: 724-731
  4. Type of Article: Article
  1. Abstract:

    We generated a transgenic mouse strain (LSL-T beta RICA) containing a latent constitutively active TGF beta type I receptor (T beta RI/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 P-actin) promoter, is repressed by a floxed transcriptional "Stop" (LSL, Lox-Stop-Lox). In the presence of crerecombinase, the "Stop" is excised to allow T beta RICA transgene expression. We showed that restricted expression of T beta RICA in T lymphocytes efficiently activates TGFP signaling and rescues the T-cell autoimmune disorders of TGF beta RII conditional knockouts. Unexpectedly, our study reveals that TGFP signaling upregulation controls T-cell activation but does not impair their development or their peripheral homeostasis. In addition to the information provided on TGF beta effects on T-cell biology, LSL-T beta RICA mouse constitutes an attractive tool to address the effect of TGFP signaling upregulation in any cell type expressing the cre-recombinase. genesis 46:724-731, 2008. Published 2008 Wiley-Liss, Inc.

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External Sources

  1. PMID: 18821589

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