Creation and Use of a Cre Recombinase Transgenic Database

Embryonic stem (ES) cell-mediated transgenic approaches have revolutionized mammalian genetics in the last decade. Close to 4000 genes have been targeted to date. Analysis of these genetic alterations has provided an unprecedented understanding of critical gene functions that underlie normal developmental and disease mechanisms in mammals. We have also learned, however, that mammalian genetic determination is complex: genes have multiple functions during the life of an individual. In addition, mammalian genetic determination often utilizes gene families, in which the members have similar structure and overlapping expression and functions. These two phenomena pointed out some limitations of the gene-targeting approach. In many cases a gene “knockout” resulted in early embryonic lethality, which obscured the study of potential later functions. In other cases the “knockout” did not have any phenotype due to the compensation of the gene deficiency by other family members. These limitations have called for further development of the powerful gene-targeting technology (1 –3 ).