Animal Biotechnology and Modeling
223
practices are well documented and used
to optimize production of transgenic rats
and rabbits.
In some cases, speciFc physiological
characteristics unique to a species have
made it a more appropriate or successful
model for a particular disease; such was
the case for lines of transgenic rats exhibit-
ing hypertension-induced symptoms and
pathology resulting from overexpression
of speciFc transgenes (viz. a mouse
Ren
-2
renin transgene or a human angiotensino-
gen gene construct) that were not similarly
expressed in transgenic mice.
Both transgenic rats and rabbits have
provided models for the study of speciFc
cancers: transgenic rats expressing an SV-
40 T-antigen construct controlled by an
albumin promoter develop hepatocellular
carcinomas. Transgenic rabbits in which
expression of a c-
myc
transgene construct
is driven by a rabbit immunoglobulin
enhancer exhibit malignant lymphocytic
leukemia.
Particular
strains
of
rabbits
have historically served as models for the
study of lipid and lipoprotein metabolism.
In
this
tradition,
lines
of
transgenic
rabbits bearing human apolipoprotein A-I
antisense transgenes have been generated
for the study of the biosynthesis of high
density lipoproteins.
±inally, several studies have proven rab-
bits to be acceptable models for ‘‘gene
pharming.’’ In these experiments, foreign
proteins are expressed in transgenic an-
imals, preferentially in mammary tissue,
and are secreted into milk, from which
they can be readily puriFed. Rabbits are
considered to be suitable models for such
use for three reasons: lactating females
produce relatively large volumes of milk
daily, rabbit milk possesses a high protein
concentration, and they tend to nurse their
offspring infrequently. To date, transgenic
rabbits have been separately produced, in
which human proteins (e.g.
α
1
-antitrypsin,
interleukin
2,
growth
hormone,
tissue
plasminogen
activator)
and
bovine
α
-
lactalbumin have been expressed in mam-
mary tissue and harvested from milk.
3
Production of Transgenic Domestic Animals
3.1
Overview
The success of transgenic mouse experi-
ments led a number of research groups
to study the transfer of similar gene con-
structs into the germ line of domestic ani-
mal species. These efforts have focused on
addressing one of the three research goals:
improving the productivity traits of domes-
tic food animal species, development of
transgenic animals for use as bioreactors
(i.e. producers of recoverable quantities of
medically or biologically important pro-
teins), and in developing tissues, organs,
or reagents for transplantation-related end-
points. Toward these goals, a number of
strategies have been employed to date.
Such strategies run the gamut from molec-
ular modeling (systems designed to study
dominant gene expression, homologous
recombination/gene targeting and the use
of ES cells) to cell biology (efFciency of
transformation of eggs or cells) to block-
ing or ablating gene function (disruption
of gene expression by antisense or RNAi
transgene
constructs,
gene
ablation
or
knockout models). Since 1985, numer-
ous studies have focused on transgenic
farm animals created using growth-related
gene constructs. Unfortunately, for the
most part, deleterious consequences of
various manipulations have failed to iden-
tify commercially useful animals because
of an inability to coordinately regulate
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