[Transgenic mice: a major advance in biomedical research]

Transgenic mice bear stable, artificially induced genetic modifications that are transmitted to their offspring. They are prepared from cultured embryonic stem cells isolated from blastocysts. The stem cells are then transfected with a vector comprising a selection cassette and the sequence to be introduced, modified or suppressed, lying between two sequences identical to those flanking the target gene. The target gene is thereby "knocked out" and replaced by the selection cassette, through homogeneous recombination. Cells in which recombination has successfully taken place are sorted by detecting the selection cassette, and are injected into an embryo. This results in so-called mosaic mice which, after crossing, will give birth to mice that are either heterozygous or homozygous for the knocked out gene. A variety of genomic modifications can be obtained with this approach, including gene knock-out, insertion of multiple gene copies, introduction of a reporter gene under the control of the promoter of the gene of interest, and "conditional" mutations that are expressed in a given tissue or for a specific period of time. Transgenic mice can be used to examine the phenotype resulting from a null mutation or from the introduction of multiple gene copies, as well as factors controlling the synthesis of a specific protein, the phenotypic consequences of point mutations, and the genes involved in embryo development. Institutes have been created specifically to phenotype transgenic mice, frequently using non invasive techniques. The results thus obtained are collected in databases, thus allowing scientists to determine the minimal number of animals necessary for a given experiment.