| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
1
* The Albert Einstein Cancer Center,
Department of Developmental and Molecular Biology,
Department of Medicine and
§ Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA;
¶ Smith College Lyman Conservatory, Northampton, Massachusetts 01636, USA;
|| Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
1Correspondence: The Albert Einstein Cancer Center, Departments of Medicine, and Developmental and Molecular Biology, Albert Einstein College of Medicine, Chanin 302, 1300 Morris Park Ave, Bronx, New York 10461, USA. E-mail pestell{at}aecom.yu.edu
The ability to regulate temporal- and spatial-specific expression of
target genes in transgenic mice will facilitate analysis of gene
function and enable the generation of murine models of human diseases.
The genetic analysis of mammary gland tumorigenesis requires the
development of mammary gland-specific transgenics, which are tightly
regulated throughout the adult mammary epithelium. Analysis of genes
implicated in mammary gland tumorigenesis has been hampered by mosaic
transgene expression and the findings that homozygous deletion of
several candidate genes (cyclin D1,
Stat5A, prolactin receptor) abrogates
normal mammary gland development. We describe the development of
transgenic mouse lines in which sustained transgene expression was
inducibly regulated, both specifically and homogeneously, in the adult
mammary gland epithelium. Transgenes encoding RXR
and a chimeric
ecdysone receptor under control of a modified MMTV-LTR, which targets
mammary gland expression, were used. These transgenic ‘receptor’
lines were crossed with transgenic ‘enhancer’ lines in which the
ecdysone/RXR binding site induced ligand-dependent expression of
transgenic ß-galactosidase. Pharmacokinetic analysis of a highly
bioactive ligand (ponasterone A), identified through screening
ecdysteroids from local plants, demonstrated sustained release and
transgene expression in vivo. This transgenic model with
both tightly regulated and homogeneous transgene expression, which was
sustained in vivo using ligands readily extracted from
local flora, has broad practical applicability for genetic analysis of
mammary gland disease.—Albanese, C., Reutens, A. T., Bouzahzah,
B., Fu, M., D’amico, M., Link, T., Nicholson, R., Depinho, R. A.,
Pestell, R. G. Sustained mammary gland-directed, ponasterone
A-inducible expression in transgenic mice.
Key Words: ecdysteroids • gland-specific transgenics • DNA binding site
This article has been cited by other articles:
|
|
 |
|
  K. Wu, S. Katiyar, A. Li, M. Liu, X. Ju, V. M. Popov, X. Jiao, M. P. Lisanti, A. Casola, and R. G. Pestell Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8 PNAS, May 13, 2008; 105(19): 6924 - 6929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wu, A. Li, M. Rao, M. Liu, V. Dailey, Y. Yang, D. Di Vizio, C. Wang, M. P. Lisanti, G. Sauter, et al. DACH1 Is a Cell Fate Determination Factor That Inhibits Cyclin D1 and Breast Tumor Growth. Mol. Cell. Biol., October 1, 2006; 26(19): 7116 - 7129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sakamaki, M. C. Casimiro, X. Ju, A. A. Quong, S. Katiyar, M. Liu, X. Jiao, A. Li, X. Zhang, Y. Lu, et al. Cyclin d1 determines mitochondrial function in vivo. Mol. Cell. Biol., July 1, 2006; 26(14): 5449 - 5469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hulit, C. Wang, Z. Li, C. Albanese, M. Rao, D. Di Vizio, S. Shah, S. W. Byers, R. Mahmood, L. H. Augenlicht, et al. Cyclin D1 Genetic Heterozygosity Regulates Colonic Epithelial Cell Differentiation and Tumor Number in ApcMin Mice Mol. Cell. Biol., September 1, 2004; 24(17): 7598 - 7611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D'Amico, K. Wu, M. Fu, M. Rao, C. Albanese, R. G. Russell, H. Lian, D. Bregman, M. A. White, and R. G. Pestell The Inhibitor of Cyclin-Dependent Kinase 4a/Alternative Reading Frame (INK4a/ARF) Locus Encoded Proteins p16INK4a and p19ARF Repress Cyclin D1 Transcription through Distinct cis Elements Cancer Res., June 15, 2004; 64(12): 4122 - 4130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Li, Z. Yang, J. Hou, A. McCracken, M. A. Jennings, and M. Y. J. Ma Compromised Reproductive Function in Adult Female Mice Selectively Expressing Mutant ErbB-1 Tyrosine Kinase Receptors in Astroglia Mol. Endocrinol., November 1, 2003; 17(11): 2365 - 2376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wang, N. Pattabiraman, J. N. Zhou, M. Fu, T. Sakamaki, C. Albanese, Z. Li, K. Wu, J. Hulit, P. Neumeister, et al. Cyclin D1 Repression of Peroxisome Proliferator-Activated Receptor {gamma} Expression and Transactivation Mol. Cell. Biol., September 1, 2003; 23(17): 6159 - 6173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bockamp, M. Maringer, C. Spangenberg, S. Fees, S. Fraser, L. Eshkind, F. Oesch, and B. Zabel Of mice and models: improved animal models for biomedical research Physiol Genomics, December 3, 2002; 11(3): 115 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. GUNTHER, G. K. BELKA, G. B. W. WERTHEIM, J. WANG, J. L. HARTMAN, R. B. BOXER, and L. A. CHODOSH A novel doxycycline-inducible system for the transgenic analysis of mammary gland biology FASEB J, March 1, 2002; 16(3): 283 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Mills Changing colors in mice: an inducible system that delivers Genes & Dev., June 15, 2001; 15(12): 1461 - 1467. [Full Text] [PDF]
|
|
|
|
|
|
E. Saez, M. C. Nelson, B. Eshelman, E. Banayo, A. Koder, G. J. Cho, and R. M. Evans Identification of ligands and coligands for the ecdysone-regulated gene switch PNAS, December 8, 2000; (2000) 260499497. [Abstract] [Full Text]
|
|
|
|
|
|
E. Saez, M. C. Nelson, B. Eshelman, E. Banayo, A. Koder, G. J. Cho, and R. M. Evans Identification of ligands and coligands for the ecdysone-regulated gene switch PNAS, December 19, 2000; 97(26): 14512 - 14517. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
