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

被引：39
作者：
Bartholin, Laurent [1 ,2 ]
Cyprian, Farhan S. [2 ,3 ,4 ]
Vincent, David [2 ]
Garcia, Celine N. [2 ,3 ,4 ]
Martel, Sylvie
Horvat, Branka [2 ,3 ,4 ]
Berthet, Cyril [5 ]
Goddard-Leon, Sophie
Treilleux, Isabelle
Rimokh, Ruth [2 ]
Marie, Julien C. [2 ,3 ,4 ]
机构：
[1] Ctr Leon Berard, INSERM, Avenir Grp, U590,IFR62, F-69373 Lyon 08, France
[2] Univ Lyon 1, F-69365 Lyon, France
[3] INSERM, U758, IFR128, F-69008 Lyon, France
[4] ENS, Lyon, France
[5] NIH, Ctr Canc Res, Frederick, MD USA
来源：
GENESIS | 2008年 / 46卷 / 12期
关键词：
TGF beta; receptor; lymphocyte; transgenesis; mouse; Smad;
D O I：
10.1002/dvg.20425
中图分类号：
Q [生物科学];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
We generated a transgenic mouse strain (LSL-T beta RI(CA)) 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 RI(CA) transgene expression. We showed that restricted expression of T beta RI(CA) 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 RI(CA) 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.
引用
收藏
页码：724 / 731
页数：8
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