Animal Biotechnology
Animal biotechnology is the application
of scientific and engineering principles
to the processing or production of materials
by animals or aquatic species to provide
goods and services (NRC 2003). Examples of
animal biotechnology include generation of
transgenic animals or transgenic fish (animals
or fish with one or more genes introduced
by human intervention), using gene knockout
technology to generate animals in which a
specific gene has been inactivated, production
of nearly identical animals by somatic cell
nuclear transfer (also referred to as clones),
or production of infertile aquatic species.
Transgenics
Since the early 1980s, methods have been
developed and refined to generate transgenic
animals or transgenic aquatic species. For
example, transgenic livestock and transgenic
aquatic species have been generated with
increased growth rates, enhanced lean muscle
mass, enhanced resistance to disease or improved
use of dietary phosphorous to lessen the
environmental impacts of animal manure. Transgenic
poultry, swine, goats, and cattle also have
been produced that generate large quantities
of human proteins in eggs, milk, blood, or
urine, with the goal of using these products
as human pharmaceuticals. Examples of human
pharmaceutical proteins include enzymes,
clotting factors, albumin, and antibodies.
The major factor limiting widespread use
of transgenic animals in agricultural production
systems is the relatively inefficient rate
(success rate less than 10 percent) of production
of transgenic animals. NIFA has supported research
projects to generate transgenic animals or
transgenic aquatic species with enhanced
production or health traits.
Gene Knockout Technology
Animal biotechnology also can knock out or
inactivate a specific gene. Knockout technology
creates a possible source of replacement organs
for humans. The process of transplanting cells,
tissues, or organs from one species to another
is referred to as “xenotransplantation.” Currently,
the pig is the major animal being considered
as a xenotransplant donor to humans. Unfortunately,
pig cells and human cells are not immunologically
compatible. Pig cells express a carbohydrate
epitope (alpha1, 3 galactose) on their surface
that is not normally found on human cells.
Humans will generate antibodies to this epitope,
which will result in acute rejection of the
xenograft. Genetic engineering is used to knock
out or inactivate the pig gene (alpha1, 3 galactosyl
transferase) that attaches this carbohydrate
epitope on pig cells. Other examples of knockout
technology in animals include inactivation
of the prion-related peptide (PRP) gene that
may generate animals resistant to diseases
associated with prions (bovine spongiform encephalopathy
[BSE], Creutzfeldt-Jakob Disease [CJD], scrapie,
etc.). Most of the funding for these types
of projects is conducted by private companies
or in academic laboratories supported by the National
Institutes of Health. Research projects
designed to provide basic information regarding
mechanisms associated with gene
knockout technology are supported by NIFA.
Somatic Cell Nuclear Transfer
Another application of animal biotechnology is the use of somatic cell nuclear
transfer to produce multiple copies of animals that are nearly identical copies
of other animals (transgenic animals, genetically superior animals, or animals
that produce high quantities of milk or have some other desirable trait, etc.).
This process has been referred to as cloning. To date, somatic cell nuclear transfer
has been used to clone cattle, sheep, pigs, goats, horses, mules, cats, rats,
and mice. The technique involves culturing somatic cells from an appropriate
tissue (fibroblasts) from the animal to be cloned. Nuclei from the cultured somatic
cells are then microinjected into an enucleated oocyte obtained from another
individual of the same or a closely related species. Through a process that is
not yet understood, the nucleus from the somatic cell is reprogrammed to a pattern
of gene expression suitable for directing normal development of the embryo. After
further culture and development in vitro, the embryos are transferred to a recipient
female and ultimately will result in the birth of live offspring. The success
rate for propagating animals by nuclear transfer is often less than 10 percent
and depends on many factors, including the species, source of the recipient ova,
cell type of the donor nuclei, treatment of donor cells prior to nuclear transfer,
the techniques employed for nuclear transfer, etc. NIFA has supported research
projects to obtain a better understanding of the basic cellular mechanisms associated
with nuclear
reprogramming.
Production of Infertile Aquatic Species. In aquaculture production systems, some
species are not indigenous to a given area and can pose an ecological risk to
native species should the foreign species escape confinement and enter the natural
ecosystem. Generation of large populations of sterile fish or mollusks is one
potential solution to this problem. Techniques have been developed to alter the
chromosome complement to render individual fish and mollusks infertile. For example,
triploid individuals (with three, instead of two, sets of chromosomes) have been
generated by using various procedures to interfere with the final step in meiosis
(extrusion of the second polar body). Timed application of high or low temperatures,
various chemicals, or high hydrostatic pressure to newly fertilized eggs has
been effective in producing triploid individuals. At a later time, the first
cell division of the zygote can be suppressed to produce a fertile tetraploid
individual (four sets of chromosomes). Tetraploids can then be mated with normal
diploids to produce large numbers of infertile triploids. Unfortunately, in a
commercial production system, it is often difficult to obtain sterilization of
100 percent of the individuals; thus, alternative methods are needed to ensure
reproductive confinement of transgenic fish. Another technique that is being
developed for finfish is to farm monosex fish stocks. Monosex populations can
be produced by gender reversal and progeny testing to identify XX males for producing
all female stocks or YY males for producing all male stocks. NIFA has supported research
projects to alter the chromosome content or produce monosex populations of
genetically engineered fish or mollusks.
As with any new technology, animal biotechnology faces a variety of uncertainties,
safety issues and potential risks. For example, concerns have been raised regarding:
the use of unnecessary genes in constructs used to generate transgenic animals,
the use of vectors with the potential to be transferred or to otherwise contribute
sequences to other organisms, the potential effects of genetically modified
animals on the environment, the effects of the biotechnology on the welfare
of the animal, and potential human health and food safety concerns for meat
or animal products derived from animal biotechnology. Before animal biotechnology
will be used widely by animal agriculture production systems, additional research
will be needed to determine if the benefits of animal biotechnology outweigh
these potential risks. The USDA Biotechnology Risk Assessment Grants program
supports environmental risk assessment research projects on genetically engineered
animals. In addition, the NRI Animal
Protection program supports research projects to determine the effects
of genetic modification on the health and well-being of the animal.
Advances in animal biotechnology have been facilitated by recent progress
in sequencing and analyzing animal genomes, identification of molecular markers
(microsatellites, expressed sequence tags [ESTs], quantitative trait loci [QTLs],
etc.) and a better understanding of the mechanisms that regulate gene expression.
For more information on these topics and projects supported by NIFA in this
area, see Animal
Breeding, Genetics, and Genomics.
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