The Cre-loxP based chromosome engineering strategy. 5′ hprt was previously named hprtΔ3′; 3′ hprt was previously name hprtΔ5′. A neomycin (Neo) or a puromycin (Puro) resistance gene is linked to the first or the second loxP site, respectively, for positive selection during gene targeting. In this case, Cre recombination between two loxP sites targeted in the same orientation in cis (on the same chromosome) leads to a deletion that is neomycin and puromycin sensitive due to the loss of the Neo- and Puro-carrying reciprocal product, a ring chromosome in G1 (shown) or a duplication sister chromatid in G2 (not shown). If the two loxP sites are on the two different chromosome homologues (in trans), a deletion and a duplication will be produced. The rearrangements can then be transmitted through the mouse germline if viable.