212
Animal Biotechnology and Modeling
integrated into their genome) are referred
to as ‘‘transgenic,’’ a term Frst coined
by Gordon and Ruddle in 1981. As such,
transgenic animals are recognized as spe-
ciFc species variants or strains, which
result from the introduction and integra-
tion of new gene(s), or ‘‘transgenes,’’ into
the genome. More recently, the term
trans-
genic
has been extended to chimeric or
knockout
mice in which researchers have
selectively removed or modiFed a gene or
genes within the host genome.
±or
years,
many
studies
were
envi-
sioned – if only an animal genome could
be readily modiFed. The realization of
the many technologies at hand today has
opened numerous avenues for research.
Production of transgenic mice has marked
the convergence of earlier advances in
the areas of recombinant DNA technol-
ogy and the manipulation and culture of
animal germ plasm (±ig. 1). Transgenic
mice provide powerful models to explore
the regulation of gene expression as well
as the regulation of cellular and physio-
logical processes. The use of transgenic
animals in biomedical, agricultural, and
biotechnological Felds requires the ability
to target gene incorporation and to control
the timing and level of transgene expres-
sion. Experimental designs have taken
advantage of the ability to direct speciFc
(e.g. cell, tissue, organ speciFcity) as well
as ubiquitous (whole-body) expression
in
vivo
. ±urthermore, from embryology to
virology, transgenic technology provides
unique animal models for studies in vari-
ous disciplines that would otherwise be all
but impossible to develop spontaneously.
1.2
Applications of Transgenic Animals
A number of methods exist for gene
transfer in mammalian species, including
DNA
microinjection,
embryonic
stem
(ES)
cell
transfer,
retroviral
infection,
blastomere/embryo
aggregation,
terato-
carcinoma
cell
transfer,
electrofusion,
nuclear transplantation,
spermatogonial
cell transfer, and perhaps spermatozoa-
mediated transfer.
Transgenic
technology
has
been
ex-
tended to a variety of animal species in
addition to the mouse, including rats, rab-
b
i
ts
,sw
ine
,rum
inan
ts(sheep
,goa
ts
,and
cattle), poultry, and Fsh. Transgenic am-
phibians, insects, nematodes, and mem-
bers of the plant kingdom have also been
produced. With advances in the under-
standing of promoter/enhancer elements
and transcription/regulatory proteins in-
volved in the control of gene expression,
the technology continues to evolve using
different model systems (Table 1). In the
systems explored to date, gene-transfer
technology is a proven asset in science
as a means of dissecting gene regula-
tion and expression
in vivo
.A
ss
u
c
h
,
the primary questions that are addressed,
concern the roles of individual genes in de-
velopment or in particular developmental
Tab. 1
Applications of transgenic mice.
Transgenic mice have provided models in
biomedical, veterinary, agricultural, and
biotechnological disciplines in the study of
gene expression and developmental biology,
as well as for
the Felds of embryology, endocrinology,
genetics, immunology, neurology, oncology,
pathology, physiology, toxicology, and
virology;
the study of genetic bases of disease, and the
design and testing of therapeutic strategies;
gene therapy;
disease resistance in humans and animals;
drug and product efFcacy testing/screening;
novel product development through
‘‘molecular pharming’’
previous page 212 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 214 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off