Generation of Mice With a Conditional Allele for Transforming Growth Factor beta 1 Gene

被引:42
作者
Azhar, Mohamad [1 ,2 ]
Yin, Moying [3 ]
Bommireddy, Ramireddy [1 ,4 ]
Duffy, John J. [3 ]
Yang, Junqi [5 ]
Pawlowski, Sharon A. [3 ]
Boivin, Gregory P. [6 ]
Engle, Sandra J. [7 ]
Sanford, L. P. [1 ]
Grisham, Christina [3 ]
Singh, Ram R. [8 ]
Babcock, George F. [9 ,10 ]
Doetschman, Thomas [1 ,2 ]
机构
[1] Univ Arizona, Inst BIO5, Tucson, AZ USA
[2] Univ Arizona, Dept Cell Biol, Tucson, AZ USA
[3] Univ Cincinnati, Dept Mol Genet, Cincinnati, OH USA
[4] Univ Arizona, Dept Immunobiol, Tucson, AZ USA
[5] Univ Cincinnati, Dept Canc & Cell Biol, Cincinnati, OH USA
[6] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH USA
[7] Pfizer Inc, Groton, CT 06340 USA
[8] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA
[9] Univ Cincinnati, Dept Surg, Cincinnati, OH 45267 USA
[10] Shriners Hosp Children, Cincinnati, OH USA
基金
美国国家卫生研究院;
关键词
transforming growth factor beta; conditional knockout mice; TGF-BETA; EXPRESSION PATTERNS; II RECEPTOR; IN-VIVO; TGF-BETA-1; GROWTH-FACTOR-BETA-1; CELLS; ACTIVATION; DIFFERENTIATION; LYMPHOCYTES;
D O I
10.1002/dvg.20516
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transforming growth factor beta 1 (TGF beta 1) is a multifunctional growth factor involved in wound healing, tissue fibrosis, and in the pathogenesis of many syndromic diseases (e.g., Marfan syndrome, Camurati-Engelmann disease) and muscular, neurological, ophthalmic, cardiovascular and immunological disorders, and cancer. Since the generation of Tgfb1 knockout mice, there has been extraordinary progress in understanding its physiological and pathophysiological function. Here, we report the generation of a conditional knockout allele for Tgfb1 in which its exon 6 is flanked with LoxP sites. As proof of principle, we crossed these mice to LckCre transgenic mice and specifically disrupted Tgfb1 in T cells. The results indicate that T-cell-produced TGF beta 1 is required for normal in vivo regulation of peripheral T-cell activation, maintenance of T-cell homeostasis, and suppression of autoimmunity. genesis 47:423-431, 2009. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:423 / 431
页数:9
相关论文
共 31 条
[1]   Transforming growth factor beta in cardiovascular development and function [J].
Azhar, M ;
Schultz, JEJ ;
Grupp, I ;
Dorn, GW ;
Meneton, P ;
Molin, DGM ;
Gittenberger-de Groot, AC ;
Doetschman, T .
CYTOKINE & GROWTH FACTOR REVIEWS, 2003, 14 (05) :391-407
[2]   Gene Targeted Ablation of High Molecular Weight Fibroblast Growth Factor-2 [J].
Azhar, Mohamad ;
Yin, Moying ;
Zhou, Ming ;
Li, Hongqi ;
Mustafa, Marwan ;
Nusayr, Eyad ;
Keenan, Jack B. ;
Chen, Hwudaurw ;
Pawlosky, Sharon ;
Gard, Connie ;
Grisham, Christina ;
Sanford, L. Philip ;
Doetschman, Tom .
DEVELOPMENTAL DYNAMICS, 2009, 238 (02) :351-357
[3]   TGFβ1 inhibits Ca2+-calcineurin-mediated activation in thymocytes [J].
Bommireddy, R ;
Ormsby, I ;
Yin, M ;
Boivin, GP ;
Babcock, GF ;
Doetschman, T .
JOURNAL OF IMMUNOLOGY, 2003, 170 (07) :3645-3652
[4]   TGF-β1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes [J].
Bommireddy, R ;
Saxena, V ;
Ormsby, I ;
Yin, MY ;
Boivin, GP ;
Babcock, GF ;
Singh, RR ;
Doetschman, T .
JOURNAL OF IMMUNOLOGY, 2003, 170 (09) :4612-4622
[5]   TGFβ1 and Treg cells:: alliance for tolerance [J].
Bommireddy, Ramireddy ;
Doetschman, Thomas .
TRENDS IN MOLECULAR MEDICINE, 2007, 13 (11) :492-501
[6]   Differentiation plasticity regulated by TGF-β family proteins in development and disease [J].
Derynck, Rik ;
Akhurst, Rosemary J. .
NATURE CELL BIOLOGY, 2007, 9 (09) :1000-1004
[7]  
DICKSON MC, 1995, DEVELOPMENT, V121, P1845
[8]  
Engle SJ, 1999, CANCER RES, V59, P3379
[9]   ABNORMAL LUNG DEVELOPMENT AND CLEFT-PALATE IN MICE LACKING TGF-BETA-3 INDICATES DEFECTS OF EPITHELIAL-MESENCHYMAL INTERACTION [J].
KAARTINEN, V ;
VONCKEN, JW ;
SHULER, C ;
WARBURTON, D ;
BU, D ;
HEISTERKAMP, N ;
GROFFEN, J .
NATURE GENETICS, 1995, 11 (04) :415-421
[10]   PRODUCTION OF TRANSFORMING GROWTH-FACTOR-BETA BY HUMAN LYMPHOCYTES-T AND ITS POTENTIAL ROLE IN THE REGULATION OF T-CELL GROWTH [J].
KEHRL, JH ;
WAKEFIELD, LM ;
ROBERTS, AB ;
JAKOWLEW, S ;
ALVAREZMON, M ;
DERYNCK, R ;
SPORN, MB ;
FAUCI, AS .
JOURNAL OF EXPERIMENTAL MEDICINE, 1986, 163 (05) :1037-1050