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

被引：40

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 [理学]; 0710 [生物学]; 09 [农学];

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

页码：724 / 731

页数：8

共 25 条

[1]

FLRG, an activin-binding protein, is a new target of TGFβ transcription activation through Smad proteins [J].