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J. Biol. Chem., Vol. 277, Issue 15, 13099-13105, April 12, 2002
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From the Departments of Pediatrics and § Medicine,
Stanford University Medical Center, Stanford, California 94305
Lactase gene transcription is spatially
restricted to the proximal and middle small intestine of the developing
mouse. To identify regions of the lactase gene involved in mediating
the spatiotemporal expression pattern, transgenic mice harboring 0.8-, 1.3-, and 2.0-kb fragments of the 5'-flanking region cloned upstream of
a firefly-luciferase reporter were generated. Transgene expression was
assessed noninvasively in living mice using a sensitive low light
imaging system. Two independent, 1.3- and 2.0-kb, lactase promoter-reporter transgenic lines expressed appropriate high levels of
luciferase activity in the small intestine (300-3,000 relative light
units/µg) with maximal expression in the middle segments. Post-weaned
30-day transgenic offspring also demonstrated an appropriate 4-fold
maturational decline in luciferase expression in the small intestine.
The pattern of the 2.0-kb promoter transgene mRNA abundance most
closely mimicked that of the endogenous lactase gene with respect to
spatiotemporal restriction. In contrast, a 0.8-kb promoter-reporter
construct expressed low level luciferase activity (<25 relative light
units/µg) in multiple organs and throughout the gastrointestinal
tract in transgenic mice. Thus, a distinct 5'-region of the
lactase promoter directs intestine-specific expression in the small
intestine of transgenic mice, and regulatory sequences have been
localized to a 1.2-kb region upstream of the lactase transcription
start site. In addition, we have demonstrated that in
vivo bioluminescence imaging can be utilized for assessment of
intestinal expression patterns of a luciferase reporter gene driven by
lactase promoter regions in transgenic mice.
Regulation of Intestine-specific Spatiotemporal Expression by the
Rat Lactase Promoter*
,,
*
This work was supported by the NIDDKD Grant DK-02552 from
the National Institutes of Health.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Both authors contributed equally to this work.
¶
To whom correspondence should be addressed: Dept. of
Pediatrics, Stanford University School of Medicine, 750 Welch Rd., Ste. 116, Palo Alto, CA 94304. Tel.: 650-723-5070; Fax: 650-498-5608; E-mail: erc@stanford.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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