Two large insert vectors, lambda PS and lambda KO, facilitate rapid mapping and targeted disruption of mammalian genes.

The construction and the testing of two λ phage vectors are described that greatly simplify the tasks of mapping genomic DNA and making replacement-type gene-targeting vectors for mammalian cells from a library of isogenic genomic DNA. This first vector, λPS, accommodates up to 20 kb and allows inserts to be automatically subcloned in plasmid form because of the presence of loxP sites flanking the insert. The second vector, λKO, accommodates up to 16.7 kb and allows inserts to be automatically subcloned as plasmids containing HSVtk genes that are positioned flanking the inserted genomic DNA