This chapter provides an insight into the mammalian life between fertilization and implantation gained from researches of transgenic mouse models. Transgenic mouse technology refers to the incorporation of engineered DNA into the heritable mouse genome. The genetic alteration can be accomplished through microinjection of a transgene into the male pronucleus of one-cell embryos, viral infection of early mouse embryos or ES cells, or targeted mutagenesis of ES cells. Oocytes microinjected with DNA are expected to incorporate concatamers of the engineered transgene and develop into founder mice with the potential to both pass on the transgene and express the gene product encoded. These F0 mice and their mutant F1 progeny are known as hemizygous mice because the transgene integration creates a new allele within the genome, random in its location and effects on any neighboring genes. In contrast, mutagenized ES cells can be made to harbor targeted mutations; researchers can deliberately replace a portion of the genome with a "look-alike" construct and selection for nonrandom integration. The resulting heterozygote ES cells are maintained in pluripotent states in vitro and may be "reintroduced" into blastocyst-stage embryos by injection into the blastocoel to give rise to chimeric mice, which represent a mixture of cell lineages derived from the manipulated ES cells and the original inner cell mass (ICM). When the ES cell line contributes to gamete development in the resulting chimeras, this allows the establishment of mutant lines for use as research models.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)