Hypertension, Vol 22, 599-607, Copyright © 1993 by American Heart Association
CD Sigmund
Over the past decade, the development of gene-transfer technology in whole
animals has afforded unprecedented opportunities for investigators to probe
complex regulatory systems in vivo. Important advances in our understanding
of the mechanisms of gene expression and regulation and the development of
animal models of human diseases are but two examples of how this technology
has affected medical science. Transgenic animals are defined as animals in
which a segment of DNA has been physically integrated into the genome of
all cells, including the germ line, so that it can be transmitted to
offspring as a simple Mendelian trait. The DNA segment generally consists
of a whole cloned gene, cDNA, or a novel gene modified by recombinant DNA
methodologies. Whole genomic clones of genes are often used to study
tissue- and cell- specific expression and regulation or can be used to
overexpress a gene product. Alternatively, the coding region of one gene
can be fused to the transcriptional regulatory region of another gene,
causing it to be expressed in a new spectrum of tissues and cell types. A
number of methods can be used to introduce the DNA segment, including
direct microinjection of one-cell fertilized embryos, retroviral-mediated
transfer, or gene transfer in embryonic stem cells. The technique most
often used to generate transgenic animals and perform "gene addition"
experiments is direct microinjection. Alternatively, gene deletions or
"knockouts" are performed by gene transfer in embryonic stem cells by
specifically targeting the site of integration in the genome.(ABSTRACT
TRUNCATED AT 250 WORDS)
ARTICLES
Major approaches for generating and analyzing transgenic mice. An overview
Department of Medicine, University of Iowa College of Medicine, Iowa City 52241.
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