Abstract:The rat is a reference animal model for physiological studies and for the analysis of multigenic human diseases such as hypertension, diabetes and neurological disorders. Nuclear transfer is a useful technique to produce knock out or knock in rat for this purpose. We used MG132, a protease inhibitor that reversibly blocks the first meiotic metaphase-anaphase transition in the rat, and reconstructed nuclear transfer embryos by a quick one step manipulation method, cloned embryos were transfer into oviducts of foster mothers, several alive cloned rats were produced by this protocol, which could grew to sexual maturity and generated normal progeny. Our data highlight the importance of adapting the SCNT procedure to oocyte physiology for successful cloning, and pave the way for more extensive genetic modifications such as conditional knock-out and gene replacement which are required to produce relevant models of human diseases.