Generation and characterization of mice for conditional inactivation of Zeb1

被引:27
作者
Brabletz, Simone [1 ]
Losada, Maria Lasierra [1 ]
Schmalhofer, Otto [2 ]
Mitschke, Julia [2 ]
Krebs, Angela [1 ]
Brabletz, Thomas [1 ]
Stemmler, Marc P. [1 ]
机构
[1] Friedrich Alexander Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Dept Expt Med 1, Erlangen, Germany
[2] Univ Freiburg, Fac Med, Med Ctr, Dept Gen & Visceral Surg, Freiburg, Germany
关键词
cancer; Cre-loxP; epithelial-mesenchymal transition; metastasis; mouse embryogenesis; TRANSCRIPTION FACTORS; DELTA-EF1;
D O I
10.1002/dvg.23024
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The multizinc finger containing transcription factor ZEB1 plays crucial roles during various aspects of mammalian development and tumorigenesis. Best studied in human tumors, ZEB1 is activating the embryo-derived program of epithelial-mesenchymal transition (EMT). The aberrant activation of EMT confers an invasive metastasizing phenotype with acquisition of stem cell properties and resistance to radio- and chemotherapy. Although ZEB1 has very important functions in tumor progression, not much is known about its role in physiological contexts and during development and homeostasis. We describe the generation of Zeb1(flox/flox) mice carrying a targeted mutation for conditional Zeb1 gene inactivation and show that homozygous Zeb1-depletion in the germline results in a phenotype similar to the conventional Zeb1 knockout.
引用
收藏
页数:7
相关论文
共 13 条
[1]   EMT: 2016 [J].
Angela Nieto, M. ;
Huang, Ruby Yun-Ju ;
Jackson, Rebecca A. ;
Thiery, Jean Paul .
CELL, 2016, 166 (01) :21-45
[2]   Igf1r Signaling Is Indispensable for Preimplantation Development and Is Activated via a Novel Function of E-cadherin [J].
Bedzhov, Ivan ;
Liszewska, Ewa ;
Kanzler, Benoit ;
Stemmler, Marc P. .
PLOS GENETICS, 2012, 8 (03)
[3]   δ-EF1 is a negative regulator of Ihh in the developing growth plate [J].
Bellon, Ellen ;
Luyten, Frank P. ;
Tylzanowski, Przemko .
JOURNAL OF CELL BIOLOGY, 2009, 187 (05) :685-699
[4]   Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression [J].
Denecker, G. ;
Vandamme, N. ;
Akay, O. ;
Koludrovic, D. ;
Taminau, J. ;
Lemeire, K. ;
Gheldof, A. ;
De Craene, B. ;
Van Gele, M. ;
Brochez, L. ;
Udupi, G. M. ;
Rafferty, M. ;
Balint, B. ;
Gallagher, W. M. ;
Ghanem, G. ;
Huylebroeck, D. ;
Haigh, J. ;
van den Oord, J. ;
Larue, L. ;
Davidson, I. ;
Marine, J-C ;
Berx, G. .
CELL DEATH AND DIFFERENTIATION, 2014, 21 (08) :1250-1261
[5]   Evolutionary functional analysis and molecular regulation of the ZEB transcription factors [J].
Gheldof, Alexander ;
Hulpiau, Paco ;
van Roy, Frans ;
De Craene, Bram ;
Berx, Geert .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2012, 69 (15) :2527-2541
[6]  
Hayashi Shigemi, 2002, Gene Expression Patterns, V2, P93, DOI 10.1016/S0925-4773(02)00292-7
[7]   Impairment of T cell development in delta EF1 mutant mice [J].
Higashi, Y ;
Moribe, H ;
Takagi, T ;
Sekido, R ;
Kawakami, K ;
Kikutani, H ;
Kondoh, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (08) :1467-1479
[8]   ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types [J].
Lehmann, Waltraut ;
Mossmann, Dirk ;
Kleemann, Julia ;
Mock, Kerstin ;
Meisinger, Chris ;
Brummer, Tilman ;
Herr, Ricarda ;
Brabletz, Simone ;
Stemmler, Marc P. ;
Brabletz, Thomas .
NATURE COMMUNICATIONS, 2016, 7
[9]   Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants [J].
Miyoshi, Tomoya ;
Maruhashi, Mitsuji ;
Van De Putte, Tom ;
Kondoh, Hisato ;
Huylebroeck, Danny ;
Higashi, Yujiro .
DEVELOPMENTAL DYNAMICS, 2006, 235 (07) :1941-1952
[10]   The EMT-activator ZEB1 induces bone metastasis associated genes including BMP-inhibitors [J].
Mock, Kerstin ;
Preca, Bogdan-Tiberius ;
Brummer, Tilman ;
Brabletz, Simone ;
Stemmler, Marc P. ;
Brabletz, Thomas .
ONCOTARGET, 2015, 6 (16) :14399-14412