Faculty Collaboration Database

Appropriate tissue- and cell-specific expression of a single copy human angiotensinogen transgene specifically targeted upstream of the HPRT locus by homologous recombination. J Biol Chem 2000 Jan 14;275(2):1073-8

Date

01/08/2000

Pubmed ID

10625648

DOI

10.1074/jbc.275.2.1073

Scopus ID

2-s2.0-0033955101 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

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-a process that can be repeated utilizing other variants of this gene. We establish the validity of this approach by showing that the hAGT(hprt) mice have normal tissue- and cell-specific expression of the human angiotensinogen gene and normally produce and process the hAGT protein at physiological levels.

Author List

Cvetkovic B, Yang B, Williamson RA, Sigmund CD

Author

Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensinogen
Animals
Chromosome Mapping
Female
Gene Expression Regulation
Genetic Engineering
Genetic Variation
Genome
Humans
Hypertension
Hypoxanthine Phosphoribosyltransferase
Introns
Male
Mice
Mice, Transgenic
Organ Specificity
Recombination, Genetic
Reproducibility of Results
Stem Cells