Area of interest
Our lab is using the recently developed technique known as gene targeting to create animal models for human diseases and to identify genes that modify the progress of these diseases . The technique of gene targeting, which allows us to introduce specific changes into the genomes of experimental animals, relies on recent advances in the fields of homologous recombination and embryonic stem (ES) cell technology. The first step in this procedure, once the gene to be modified has been chosen, is to obtain corresponding genomic DNA sequences using standard cloning techniques. After introducing desired mutations into the cloned DNA using conventional molecular biology techniques, the genomic sequences are incorporated into a plasmid known as a targeting vector. When this plasmid is introduced into mouse ES cells, the altered genomic sequences are able to undergo homologous recombination with the corresponding endogenous sequences, thereby introducing the desired modifications into the mouse genome. ES cells are unique in that they can be grown in tissue culture while maintaining their totipotency. Thus, once ES cells carrying the desired mutation are identified, they can be returned to an embryo, resulting in the formation of a chimeric animal. If the embryonic stem cells participate in the formation of the germ line of the chimeric animal, the mutation will be transmitted to the chimera’s offspring, and a mouse line carrying the desired mutation will be created. The effect of this alteration can then be studied in vivo. This technology has opened an exciting new avenue for addressing numerous biological and medical problems.