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J. Biol. Chem., Vol. 277, Issue 7, 5194-5202, February 15, 2002
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From the Molecular mechanisms directing tissue-specific
expression of gonadotropin-releasing hormone (GnRH) are difficult to
study due to the paucity and scattered distribution of GnRH neurons. To
identify regions of the mouse GnRH (mGnRH) promoter that are critical
for appropriate tissue-specific gene expression, we generated transgenic mice with fragments (
Promoter Sequences Targeting Tissue-specific Gene Expression
of Hypothalamic and Ovarian Gonadotropin-releasing Hormone in
Vivo*
§¶,
, and Section of Reproductive Endocrinology and
Infertility, the Department of Obstetrics and Gynecology, and the
§ Section of Endocrinology, the Department of Pediatrics,
The University of Chicago, Chicago, Illinois 60637, and the
Department of Biomedical Science, the Shriver Center,
Waltham, Massachusetts 02452
3446/+23 bp, 2078/+23 bp, and 1005/+28 bp) of mGnRH promoter fused to the luciferase reporter gene.
The pattern of mGnRH promoter activity was assessed by measuring luciferase activity in tissue homogenates. All three 5'-fragments of
mGnRH promoter targeted hypothalamic expression of the luciferase transgene, but with the exception of the ovary, luciferase expression was absent in non-neural tissues. High levels of ovarian luciferase activity were observed in mice generated with both 2078 and 1005 bp
of promoter. Our study is the first to define a region of the GnRH gene
promoter that directs expression to both neural and non-neural tissues
in vivo. We demonstrate that DNA sequences contained within
the proximal 1005 bp of the mGnRH promoter are sufficient to direct
mGnRH gene expression to both the ovary and hypothalamus. Our results
also suggest that DNA sequences distal to 2078 bp mediate the
repression of ovarian GnRH.
*
This work was supported by grants from the Reproductive
Scientist Development Program (to H. H. K.), the American Association of Obstetricians and Gynecologists Foundation (to H. H. K.), and National Institutes of Health Grant R01 HD34551 (to S. R.).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.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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