Sperm-Mediated Gene Transfer in Agricultural Species

Joaquin Gadea1,* Francisco Alberto Garcia-Vazquez1, Sebastian Canosas1 and John Parrington2
1

University of Murcia. Spain and2University of Oxford, United Kingdom

Abstract :
The importance of transgenic farm animals resides in their usefulness for very different objectives: for
instance in human medicine (to obtain pharmaceutical products, organs for xenotransplantation, or as
models for research in gene therapy ) or for agricultural applications such as improved output of the
carcass or milk production and composition. increased growth rate, improved feed utilisation, enhanced
reproductive performance. increased prolificacy, as well as to enhance disease resistance or reduce
environmental impact. Pronuclear DNA microinjection has long been the most reliable method to
produce transgenic animals. However, although transgenic animals have been generated using this
approach. it has many limitations. Sperm Mediated Gene Transfer (SMGT) is based on the ability of
sperm to bind, internalise, and transport exogenous DNA into an oocyte during fertilisation. In this
chapter we review the state of art of SMGT in farm animals with a special emphasis on porcine and
bovine animals, with additional information related to other ruminants and horses. We evaluate the
possible applications of transgenic pigs and cattle and review the factors related to the success of SGMT
in these species and offer our own experience based on studies analyzing the main factors in porcine
and bovine SMGT.
Keywords: Transgenic Pig. Transgenic Cattle. Biomolecules production, Human diseases models,
Xenotransplantation. Artificial insemination, In vitro fertilization, ICS1, Farm animals, Recombinase,
Embryo transfer, Flow cytometrv, DNA binding.
INTRODUCTION
The term "transgenic animals" is used to denote animals with altered characteristics resulting from
direct changes to their genetic material. Genes can be manipulated artificially, so that certain
characteristics of an animal are changed, using different genetic techniques such as gene knockout (in
which genes are made inoperative), knockin (in which genes are modified) or knockdown (in which
expression of genes is reduced). The importance of transgenic farm animals resides in their usefulness
for very different objectives: for instance in human medicine (to obtain pharmaceutical products, organs
for xenotransplantation, or as models for research in gene therapy ) or for agricultural applications such
as improved output of the carcass or milk production and composition, increased growth rate, improved
feed utilisation, enhanced reproductive performance, increased prolificacy, as well as to enhance
disease resistance or reduce environmental impact [1, 2]. The mouse has served as a model mammal in
studies of human physiology or diseases, but its use as a model for humans has many limitations. For
instance, factors such as lifespan, size, similarities in physiology and possibly genomic organisation make
cattle and pigs more similar to humans than mice [3, 4] and they may provide a better model to study
human diseases. In addition cows have the advantage that they produce a great amount of milk for a
long period of time and it is relatively easy to recover secreted products of interest from their milk. In
fact, the expression of proteins with potential therapeutic applications in the milk of livestock species
appears to be one of the most attractive commercial applications of animal t -ransgenesis [5]. As an
example of this, recently some groups have reported the production of cloned transgenic cows with
high levels expression of bioactive human growth hormone, human lactoferrin or human albumin in
their milk [6-8].
Since the first reports about transgenic animals in the 1970s many applications still await solutions for
technical or ethical challenges; however, other products of transgenic livestock technology will very
soon