Plug and socket technology can be combined with Cre/loxP technology

and then:

from Detloff, P. J., J. Lewis, S. W. John, W. R. Shehee, R. Langenbach, N. Maeda and O. Smithies 1994. Deletion and replacement of the mouse adult beta-globin genes by a "plug and socket" repeated targeting strategy. Mol Cell Biol. 14:6936-6943
Lewis, J., B. Yang, P. Detloff and O. Smithies 1996. Gene modification via "plug and socket" gene targeting. J Clin Invest. 97:3-5