HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 23, 23969-23976, June 4, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/23/23969    most recent M400973200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Galijatovic, A. Articles by Tukey, R. H. Search for Related Content PubMed PubMed Citation Articles by Galijatovic, A. Articles by Tukey, R. H. Social Bookmarking                      What's this?

The Human CYP1A1 Gene Is Regulated in a Developmental and Tissue-specific Fashion in Transgenic Mice^*

Alema Galijatovic, Deirdre Beaton, Nghia Nguyen, Shujuan Chen, Jessica Bonzo, Randall Johnson¶, Shin Maeda||, Michael Karin||, F. Peter Guengerich**, and Robert H. Tukey

From the Laboratory of Environmental Toxicology, Departments of Pharmacology, Chemistry & Biochemistry, the ^||Laboratory of Gene Regulation, Department of Pharmacology, and the ^¶Department of Biology, University of California, San Diego, La Jolla, California 92093 and the ^**Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Regulation and expression of human CYP1A1 is demonstrated in transgenic mice. We have developed two transgenic mouse lines. One mouse strain (CYPLucR) carries a functional human CYP1A1 promoter (–1612 to +293)-luciferase reporter gene, and the other strain (CYP1A1N) expresses CYP1A1 under control of the full-length human CYP1A1 gene and 9 kb of flanking regulatory DNA. With CYPLucR^+/– mice, 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) and several other aryl hydrocarbon receptor ligands induced hepatocyte-specific luciferase activity. When other tissues were examined, TCDD induced luciferase activity in brain with limited induction in lung and no detectable luciferase activity in kidney. Treatment of CYP1A1N^+/– mice with TCDD resulted in induction of human CYP1A1 in liver and lung, while mouse Cyp1a1 was induced in liver, lung, and kidney. Although induced CYP1A1/Cyp1a1 could not be detected by Western blot analysis in brains from CYP1A1N^+/– mice, induction in brain was verified by detection of CYP1A1/Cyp1a1 RNA. The administration of TCDD to nursing mothers to examine the effect of lactational exposure via milk demonstrated prominent induction of luciferase activity in livers of CYPLucR^+/– newborn pups with limited induction in brain. However, TCDD treatment of adult CYPLucR^+/– mice led to a 7–10-fold induction of brain luciferase activity. Combined these results indicate that tissue-specific and developmental factors are controlling aryl hydrocarbon receptor-mediated induction of human CYP1A1.

Received for publication, January 28, 2004 , and in revised form, March 16, 2004.

^* This work was supported by United States Public Health Services Grants ES10337 (to R. J., M. K., and R. H. T.), CA55353 (to F. P. G.), and CA90426 (to F. P. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Graduate student in the Biomedical Sciences Graduate Program.

To whom correspondence should be addressed. E-mail: rtukey{at}ucsd.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. N. Operana, N. Nguyen, S. Chen, D. Beaton, and R. H. Tukey Human CYP1A1GFP Expression in Transgenic Mice Serves as a Biomarker for Environmental Toxicant Exposure Toxicol. Sci., January 1, 2007; 95(1): 98 - 107. [Abstract] [Full Text] [PDF]

				D. C. Volz, D. C. Bencic, D. E. Hinton, J. M. Law, and S. W. Kullman 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Induces Organ- Specific Differential Gene Expression in Male Japanese Medaka (Oryzias latipes) Toxicol. Sci., May 1, 2005; 85(1): 572 - 584. [Abstract] [Full Text] [PDF]

				J. A. Bonzo, S. Chen, A. Galijatovic, and R. H. Tukey Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest Mol. Pharmacol., April 1, 2005; 67(4): 1247 - 1256. [Abstract] [Full Text] [PDF]

				C. Cheung, A.-M. Yu, J. M. Ward, K. W. Krausz, T. E. Akiyama, L. Feigenbaum, and F. J. Gonzalez THE CYP2E1-HUMANIZED TRANSGENIC MOUSE: ROLE OF CYP2E1 IN ACETAMINOPHEN HEPATOTOXICITY Drug Metab. Dispos., March 1, 2005; 33(3): 449 - 457. [Abstract] [Full Text] [PDF]