Animal Biotechnology and Modeling
235
and experimental design are also impor-
tant considerations that may limit research
efforts. For most species, husbandry con-
siderations are extensive in comparison to
mouse requirements, running the gamut
from animal and record-keeping manage-
ment to female- (e.g. controlled estrus
cycles/synchronization) and male-speci±c
(e.g. sperm analysis/quantitation) require-
ments. For most nonrodent species, pro-
curement of embryos and the trauma
associated with most manipulations are
signi±cant factors. The re±nement of non-
surgical techniques for embryo collection
and transfer
would
bypass
a
huge
±-
nancial and labor requirement for many
large domestic animal species. More im-
portantly, experimental animals would no
longer be necessarily subjected to sig-
ni±cant surgical manipulations. Perhaps
recent advances, involving embryo aggre-
gation and the derivation of transgenic
mice completely from early passage ES
cells, may shed new light on novel and
ef±cient techniques.
5.2
Future Directions
For
many
species, there
are
technical
drawbacks to various genetic-engineering
technologies that are manifest in the lack
of signi±cant gene characterization and
mapping efforts. With the complexity of
the mammalian genome, this information
is critical for the determination of ap-
propriate genes to engineer and transfer,
and in providing preliminary indications
of the potential biological consequences
of genetic-engineering experimentation.
What
are
the
appropriate
genetic
tar-
gets in different species and how will
gene-targeting
manipulations
influence
mammalian development? If genetic poly-
morphisms (indicative of related genes
that code for different isoform proteins)
or
pseudogenes
are
present,
targeting
efforts can be long and arduous. For well-
characterized genomes, the identi±cation
of speci±c genetic variations or de±ciencies
may provide only a glimpse of the effort
necessary to develop in other species. Yet,
it is hoped that with current efforts focused
on the human and animal/species-speci±c
genomes, accumulating data will prove
quite informative and adaptable, inasmuch
as conserved linkage groups are highly
probable and would be exploitable.
While current experimental ef±ciencies
for transgenic animal production are rel-
atively poor, the mechanical aspects of
producing transgenic animals should not
overshadow our ability to create and evalu-
ate biologically important animal models.
Much has been learned about early devel-
opment and effects of altering the growth
cascadeaswe
l
lasotherphysio
logica
lpro-
cesses in initial transgenic animal models.
These models have had far-reaching ef-
fects and have rede±ned what is possible in
the biological, biomedical, and agricultural
sectors. While studies of transgene expres-
sion and overexpression in mammalian
models may not always correlate exactly,
nor reveal all the possible effects and
consequences when extended to human
biology, the utility of transgenic animal
models to scienti±c discovery cannot be
overestimated. The use of ES cell or related
methodologies to provide ef±cient and tar-
geted
in vivo
genetic manipulations offers
the prospects of creating profoundly useful
animal models for biomedical, biological,
and agricultural applications. However,
the road to such success will continue to
be most challenging.
See also
Gene Targeting.
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