Provided is a method for producing a non-human viable germ cell having at least one inactivated endogenous immunoglobulin (Ig) locus, comprising expressing at least one meganuclease in a germ cell, fertilized oocyte or embryo, to generate a viable germ cell having at least one inactivated endogenous Ig locus wherein said meganuclease recognizes a meganuclease target sequence present in or proximal to said endogenous Ig locus. Transgenic animals produced by the method are useful in the production of monoclonal antibodies.
