Development, Vol 105, Issue 4 707-714, Copyright © 1989 by Company of Biologists

JOURNAL ARTICLES

Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice

R Kothary, S Clapoff, S Darling, MD Perry, LA Moran and J Rossant
Division of Molecular and Developmental Biology, Mt. Sinai Hospital Research Institute, Toronto, Ontario, Canada.

Transgenic mice have been generated that express the E. coli beta-galactosidase gene under the control of the promoter from the mouse heat-shock gene, hsp68. Sequences from -664 to +113 relative to the start of transcription of the hsp68 gene were sufficient to direct stress-induced expression of the beta-galactosidase gene in adult tail tissue and various tissues of fetal stages of development. Expression was detected in situ by staining with the chromogenic substrate, X-gal. The hybrid gene was refractory to induction in preimplantation embryos until the blastocyst stage of development, as reported for the endogenous hsp68 gene. No constitutive expression was observed by in situ staining or Northern analysis at any stage of development, even in tissues that constitutively express the endogenous hsp68 gene. We conclude that the hsp68 promoter region included in the construct contains sufficient sequence information for heat and arsenite inducibility, but it does not contain sequences controlling tissue-specific expression during development. This tightly regulated inducible promoter may provide a useful tool for short-term inducible gene expression in transgenic mice.
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				F Muller, B Chang, S Albert, N Fischer, L Tora, and U Strahle Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord Development, January 5, 1999; 126(10): 2103 - 2116. [Abstract] [PDF]

				C. Lien, C Wu, B Mercer, R Webb, J. Richardson, and E. Olson Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer Development, January 1, 1999; 126(1): 75 - 84. [Abstract] [PDF]

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				R. Searcy, E. Vincent, C. Liberatore, and K. Yutzey A GATA-dependent nkx-2.5 regulatory element activates early cardiac gene expression in transgenic mice Development, January 11, 1998; 125(22): 4461 - 4470. [Abstract] [PDF]

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				M. S. Halfon, H. Kose, A. Chiba, and H. Keshishian Targeted gene expression without a tissue-specific promoter: Creating mosaic embryos using laser-induced single-cell heat shock PNAS, June 10, 1997; 94(12): 6255 - 6260. [Abstract] [Full Text] [PDF]

				Y. Kaneko, H. Nishiyama, K. Nonoguchi, H. Higashitsuji, M. Kishishita, and J. Fujita A Novel hsp110-related Gene, apg-1, That Is Abundantly Expressed in the Testis Responds to a Low Temperature Heat Shock Rather than the Traditional Elevated Temperatures J. Biol. Chem., January 31, 1997; 272(5): 2640 - 2645. [Abstract] [Full Text] [PDF]

				R Tewari, N Gillemans, A Harper, M Wijgerde, G Zafarana, D Drabek, F Grosveld, and S Philipsen The human beta-globin locus control region confers an early embryonic erythroid-specific expression pattern to a basic promoter driving the bacterial lacZ gene Development, January 12, 1996; 122(12): 3991 - 3999. [Abstract] [PDF]

				D. Song, G Chalepakis, P Gruss, and A. Joyner Two Pax-binding sites are required for early embryonic brain expression of an Engrailed-2 transgene Development, January 2, 1996; 122(2): 627 - 635. [Abstract] [PDF]

				C. Shashikant, C. Bieberich, H. Belting, J. Wang, M. Borbely, and F. Ruddle Regulation of Hoxc-8 during mouse embryonic development: identification and characterization of critical elements involved in early neural tube expression Development, January 12, 1995; 121(12): 4339 - 4347. [Abstract] [PDF]

				E Christians, E Campion, E. Thompson, and J. Renard Expression of the HSP 70.1 gene, a landmark of early zygotic activity in the mouse embryo, is restricted to the first burst of transcription Development, January 1, 1995; 121(1): 113 - 122. [Abstract] [PDF]

				M. Zhang, H. J. Kim, H. Marshall, M. Gendron-Maguire, D. A. Lucas, A. Baron, L. J. Gudas, T. Gridley, R. Krumlauf, and J. F. Grippo Ectopic Hoxa-1 induces rhombomere transformation in mouse hindbrain Development, September 1, 1994; 120(9): 2431 - 2442. [Abstract] [PDF]

				Y Echelard, G Vassileva, and A. McMahon Cis-acting regulatory sequences governing Wnt-1 expression in the developing mouse CNS Development, January 8, 1994; 120(8): 2213 - 2224. [Abstract] [PDF]

				C Logan, W. Khoo, D Cado, and A. Joyner Two enhancer regions in the mouse En-2 locus direct expression to the mid/hindbrain region and mandibular myoblasts Development, January 3, 1993; 117(3): 905 - 916. [Abstract] [PDF]

				J Rossant, R Zirngibl, D Cado, M Shago, and V Giguere Expression of a retinoic acid response element-hsplacZ transgene defines specific domains of transcriptional activity during mouse embryogenesis. Genes & Dev., August 1, 1991; 5(8): 1333 - 1344. [Abstract] [PDF]

				A M Flenniken and B R Williams Developmental expression of the endogenous TIMP gene and a TIMP-lacZ fusion gene in transgenic mice. Genes & Dev., July 1, 1990; 4(7): 1094 - 1106. [Abstract] [PDF]

				P. S. Chang, L. Li, J. McAnally, and E. N. Olson Muscle Specificity Encoded by Specific Serum Response Factor-binding Sites J. Biol. Chem., May 11, 2001; 276(20): 17206 - 17212. [Abstract] [Full Text] [PDF]

				W. Jiang, L. Zhou, B. Breyer, T. Feng, H. Cheng, R. Haydon, A. Ishikawa, and T.-C. He Tetracycline-regulated Gene Expression Mediated by a Novel Chimeric Repressor That Recruits Histone Deacetylases in Mammalian Cells J. Biol. Chem., November 21, 2001; 276(48): 45168 - 45174. [Abstract] [Full Text] [PDF]

				J. Galceran, S.-C. Hsu, and R. Grosschedl Rescue of a Wnt mutation by an activated form of LEF-1: Regulation of maintenance but not initiation of Brachyury expression PNAS, July 17, 2001; 98(15): 8668 - 8673. [Abstract] [Full Text] [PDF]