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J Biol Chem, Vol. 275, Issue 2, 1073-1078, January 14, 2000
From the Development of experimental models by genetic
manipulation in mice has proven to be very useful in determining the
significance of particular genes in the development of or
susceptibility to hypertension. Advances in molecular genetics,
transgenic mouse technology, and physiological measurements in mice
provided an opportunity to go a step further and develop models to
analyze the physiological significance of specific gene variants
potentially causing hypertension. In this report, we describe the
development of a human angiotensinogen transgenic mouse model generated
by targeting the human angiotensinogen gene upstream of the mouse HPRT
locus by homologous recombination. The main benefit of this transgenic
mouse model is that the human angiotensinogen gene is inserted into the
mouse genome as a single copy at a predefined locus and in a specific
orientation
Appropriate Tissue- and Cell-specific Expression of a Single Copy
Human Angiotensinogen Transgene Specifically Targeted Upstream of the
HPRT Locus by Homologous Recombination*
,¶
Molecular Biology Interdisciplinary Program,
the ¶ Departments of Internal Medicine and Physiology & Biophysics, and the § Department of Obstetrics and
Gynecology, The University of Iowa College of Medicine,
Iowa City, Iowa 52242
a process that can be repeated utilizing other variants of
this gene. We establish the validity of this approach by showing that
the hAGThprt mice have normal tissue- and
cell-specific expression of the human angiotensinogen gene and normally
produce and process the hAGT protein at physiological levels.
*
Funds to support this work were obtained from the National
Institutes of Health (Grants HL55006, HL48058, and DK52617) and the
American Heart Association.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.
Established Investigator of the American Heart Association
during the performance of this work. To whom correspondence should be
addressed: Chair, Molecular Biology Interdisciplinary Program, Director, Transgenic and Gene Targeting Facility, Dept. of Internal Medicine and Physiology & Biophysics, 2191 Medical Laboratory, The
University of Iowa College of Medicine, Iowa City, Iowa 52242. Tel.:
319-335-7604; Fax: 319-353-5350; E-mail: curt-sigmund@uiowa.edu.
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