Abstract
Transgenic animals are very useful models that can be utilized for the analysis of temporal and spatial gene expression in vivo. However, generation of a transgenic animal may become problematic if the presence of the transgene leads to conditions which are toxic or lethal to cell growth. In an effort to delineate the mechanism by which a specific gene contributes to cell growth and viability, an inducible and/or conditional system was established to generate transgenic animals. The systems comprise the following: (1) Selecting a specific promoter, (2) replacing a normal gene with other gene sequences (knock out), (3) promoting destruction of the mRNA (RNAi), (4) inducing and/or conditioning by drugs (Tet on/off), and (5) conditional cell knock out with cell death. The choice of system employed is dependent on the particular aim of the investigation, and may influence the final result. The inducible and conditional promoter system represents a useful experimental approach for the development of transgenic animals and the precise examination of gene function.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ryding AD, Sharp MG, Mullins JJ (2001) Conditional transgenic technologies. J Endocrinol 171:1–14
Hakamata Y, Tahara K, Uchida H, Sakuma Y, Nakamura M, Kume A, Murakami T, Takahashi M, Takahashi R, Hirabayashi M, Ueda M, Miyoshi I, Kasai N, Kobayashi E (2001) Green fluorescent protein-transgenic rat: a tool for organ transplantation research. Biochem Biophys Res Commun 286:779–785
Inoue H, Ohsawa I, Murakami T, Kimura A, Hakamata Y, Sato Y, Kaneko T, Takahashi M, Okada T, Ozawa K, Francis J, Leone P, Kobayashi E (2005) Development of new inbred transgenic strains of rats with LacZ or GFP. Biochem Biophys Res Commun 329:288–295
Hakamata Y, Murakami T, Kobayashi E (2006) “Firefly rats” as an organ/cellular source for long-term in vivo bioluminescent imaging. Transplantation 81:1179–1184
Giel-Moloney M, Krause DS, Chen G, Van Etten RA, Leiter AB (2007) Ubiquitous and uniform in vivo fluorescence in ROSA26-EGFP BAC transgenic mice. Genesis 45:83–89
Sato Y, Igarashi Y, Hakamata Y, Murakami T, Kaneko T, Takahashi M, Seo N, Kobayashi E (2003) Establishment of Alb-DsRed2 transgenic rat for liver regeneration research. Biochem Biophys Res Commun 311:478–481
Ueda S, Fukamachi K, Matsuoka Y, Takasuka N, Takeshita F, Naito A, Iigo M, Alexander DB, Moore MA, Saito I, Ochiya T, Tsuda H (2006) Ductal origin of pancreatic adenocarcinomas induced by conditional activation of a human Ha-ras oncogene in rat pancreas. Carcinogenesis 27:2497–2510
Sato Y, Endo H, Ajiki T, Hakamata Y, Okada T, Murakami T, Kobayashi E (2004) Establishment of Cre/LoxP recombination system in transgenic rats. Biochem Biophys Res Commun 319:1197–1202
Dillon CP, Sandy P, Nencioni A, Kissler S, Rubinson DA, Van Parijs L (2005) Rnai as an experimental and therapeutic tool to study and regulate physiological and disease processes. Annu Rev Physiol 67:147–173
Sato Y, Ajiki T, Inoue S, Fujishiro J, Yoshino H, Igarashi Y, Hakamata Y, Kaneko T, Murakamid T, Kobayashi E (2005) Gene silencing in rat-liver and limb grafts by rapid injection of small interference RNA. Transplantation 79:240–243
Dann CT, Alvarado AL, Hammer RE, Garbers DL (2006) Heritable and stable gene knockdown in rats. Proc Natl Acad Sci U S A 103:11246–11251
Dann CT (2007) New technology for an old favorite: lentiviral transgenesis and RNAi in rats. Transgenic Res 16:571–580
Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A 89:5547–5551
Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H (1995) Transcriptional activation by tetracyclines in mammalian cells. Science 268:1766–1769
Braudeau C, Bouchet D, Toquet C, Tesson L, Menoret S, Iyer S, Laboisse C, Willis D, Jarry A, Buelow R, Anegon I, Chauveau C (2003) Generation of heme oxygenase-1-transgenic rats. Exp Biol Med (Maywood) 228:466–471
Tesson L, Charreau B, Menoret S, Gilbert E, Soulillou JP, Anegon I (1999) Endothelial expression of Fas ligand in transgenic rats under the temporal control of a tetracycline-inducible system. Transplant Proc 31:1533–1534
Zeng H, Horie K, Madisen L, Pavlova MN, Gragerova G, Rohde AD, Schimpf BA, Liang Y, Ojala E, Kramer F, Roth P, Slobodskaya O, Dolka I, Southon EA, Tessarollo L, Bornfeldt KE, Gragerov A, Pavlakis GN, Gaitanaris GA (2008) An inducible and reversible mouse genetic rescue system. PLoS Genet 4:e1000069
Saito M, Iwawaki T, Taya C, Yonekawa H, Noda M, Inui Y, Mekada E, Kimata Y, Tsuru A, Kohno K (2001) Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nat Biotechnol 19:746–750
Machimoto T, Yasuchika K, Komori J, Ishii T, Kamo N, Shimoda M, Konishi S, Saito M, Kohno K, Uemoto S, Ikai I (2007) Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model. Transplantation 84:1233–1239
Kawasaki M, Fujino M, Li XK, Kitazawa Y, Funeshima N, Takahashi R, Ueda M, Amano T, Hakamata Y, Kobayashi E (2003) Inducible liver injury in the transgenic rat by expressing liver-specific suicide gene. Biochem Biophys Res Commun 311:920–928
Ueda M, Ando Y, Hakamata Y, Nakamura M, Yamashita T, Obayashi K, Himeno S, Inoue S, Sato Y, Kaneko T, Takamune N, Misumi S, Shoji S, Uchino M, Kobayashi E (2007) A transgenic rat with the human ATTR V30M: a novel tool for analyses of ATTR metabolisms. Biochem Biophys Res Commun 352:299–304
Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying QL, Smith A (2008) Capture of authentic embryonic stem cells from rat blastocysts. Cell 135:1287–1298
Li P, Tong C, Mehrian-Shai R, Jia L, Wu N, Yan Y, Maxson RE, Schulze EN, Song H, Hsieh CL, Pera MF, Ying QL (2008) Germline competent embryonic stem cells derived from rat blastocysts. Cell 135:1299–1310
Ueda S, Kawamata M, Teratani T, Shimizu T, Tamai Y, Ogawa H, Hayashi K, Tsuda H, Ochiya T (2008) Establishment of rat embryonic stem cells and making of chimera rats. PLoS ONE 3:e2800
Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317
Arao Y, Hakamata Y, Igarashi Y, Sato Y, Kayama F, Takahashi M, Kobayashi E, Murakami T (2009) Characterization of hepatic sexual dimorphism in Alb-DsRed2 transgenic rats Biochem Biophys Res Commun 382:46–50
Takahashi M, Hakamata Y, Murakami T, Takeda S, Kaneko T, Takeuchi K, Takahashi R, Ueda M, Kobayashi E (2003) Establishment of lacZ-transgenic rats: a tool for regenerative research in myocardium. Biochem Biophys Res Commun 305, 904–908
Iwamoto S, Kumada M, Kamesaki T, Okuda H, Kajii E, Inagaki T, Saikawa D, Takeuchi K, Ohkawara, S, Takahashi R, Ueda S, Inoue S, Tahara K, Hakamata Y, Kobayashi E (2002) Rat encodes the paralogous gene equivalent of the human histo-blood group ABO gene. Association with antigen expression by overexpression of human ABO transferase. J Biol Chem 277, 46463–46469
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Hakamata, Y., Kobayashi, E. (2010). Inducible and Conditional Promoter Systems to Generate Transgenic Animals. In: Anegon, I. (eds) Rat Genomics. Methods in Molecular Biology, vol 597. Humana Press. https://doi.org/10.1007/978-1-60327-389-3_5
Download citation
DOI: https://doi.org/10.1007/978-1-60327-389-3_5
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-60327-388-6
Online ISBN: 978-1-60327-389-3
eBook Packages: Springer Protocols