W171: Germ Cell and Embryo Development and Manipulation for the Improvement of Livestock
Statement of Issues and Justification
STATEMENT OF THE PROBLEM: Understanding of the underlying biological mechanisms and principles of methods used to produce genetically altered livestock is limited. Furthermore, most of these methods are very inefficient. These technologies will have to be substantially more efficient if we are to realize the advantages of transgenic farm animals for human food and fiber production. These advantages include the production of more desirable products, new products and increased efficiency of the utilization of natural resources.JUSTIFICATION: The development of transgenic animals used for food and fiber production has significant potential for consumers, animal producers, their communities and our environment. Potential examples of such transgenic animals are those producing a milk containing human proteins to make a more desirable human baby formula, those producing a leaner, more desirable meat, or those more efficient in growth, reproduction, wool production, or milk production including those with increased disease resistance (Wheeler and Choi, 1997). Increased efficiencies in production of animal products can be of economic benefit to both consumers and producers and have obvious advantages to the environment in terms of reduced use of natural resources.
Current procedures for the production of experimental transgenic animals involve the use of in vitro oocyte maturation, in vitro fertilization, and in vitro culture before and after gene injection (Hasler et al., 1995). This is more practical than recovery of in vivo fertilized embryos but still extremely time and labor-consuming. Currently, more than 10 hours of labor are required to produce a single gene-injected bovine embryo for recipient transfer. When this is coupled with a 20% pregnancy rate and a 12% incorporation rate of the injected gene into the cells contributing to the offspring, an estimated 5,000 hours are required to produce a single transgenic offspring. Before transgenic animals can contribute significantly to production systems, their production will have to be far more efficient. The inefficiencies occur during oocyte maturation and fertilization, during embryo culture and during the incorporation and expression of the microinjected DNA. Short and long term storage of the transgenic embryos is necessary for efficient production of transgenic animals and needs improvement as well (Hurtt et al., 1999).
The details of meiotic maturation of oocytes (particularly the details of nuclear maturation) are beginning to be understood. Much of this work has been done with mouse oocytes; yet differences are known to exist between murine oocytes and bovine, porcine, or ovine oocytes (Cran and Moor, 1989). This is just one of the areas where the proposed regional research will contribute to animal production.
Although there have been recent advances in nuclear transfer technology in livestock and laboratory species (Wilmut et al., 1997; Schnieke et al., 1997; Wakayama et al., 1998), much is still to be learned regarding the biology and application of these methods to production of transgenic animals. This technology is very inefficient at present (Wilmut et al., 1997 ) and needs improvement before it can be widely used for livestock systems. Research to increase the practicality of making transgenic animals is directly in line with FAIR95 Goal 2 ""Meet consumer needs in domestic and international markets for competitive and high-quality products from animals. Objective l. Increase efficiencies of production livestock. Objective 2. Enhance the quality of products from animals"" (Anonymous, 1993). The economic significance of transgenic animals to U.S. animal agriculture in the future cannot be estimated with any confidence. However, the livestock and dairy industries generated over 68 billion dollars of on-farm receipts in 1992 (Anonymous, 1994). Even little effects on efficiency would repay research costs several times over.
A regional research approach is an extremely advantageous means to efficiently approach these problems. Alternative approaches can be tested in multiple laboratories and the effective procedures further tested in the remaining laboratories. Oocyte and embryo procedures appear particularly laboratory dependent; for example, the optimal exposure time for vitrification of mouse oocytes and mouse blastocysts varied significantly among laboratories (Wood et al., 1993; Valdez et al., 1993; Zhu et al., 1993; Shaw et al., 1992). Improvements in nuclear transfer methods and the development of embryonic/somatic cell lines to serve as nuclei donors are other areas that would benefit from this multiple laboratory approach.
The use of transgenic and nuclear transfer approaches are also very useful experimentally for obtaining a variety of information. Some examples are insight into the cell cycle, nuclear and cytoplasmic programing or re-programming, genomic imprinting, gene expression and developmental process to name a few. This information can be used in studies to examine basic biological questions, biomedical questions, genetic questions and evolutionary questions as well as applications for agriculture.
This proposal will evaluate two areas critically important to the future success of animal biotechnology: 1) the understanding of the developmental biology and underlying biological mechanisms of fertilization and embryonic development and 2) the refinement of methods for production of genetically modified animals to improve livestock production efficiency.
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