The objective of this proposal is to produce tetraploid embryos for aggregation with nuclear transfer embryos for the production of transgenic cattle and goats. GTC Biotherapeutics (formerly Genzyme Transgenics Corporation) has developed the expression of recombinant proteins in the milk of transgenic dairy animals. The milk of transgenic goats and cattle is a safe, abundant and cost effective production source for human biopharmaceuticals. GTC Biotherapeutics has nearly two-dozen commercial transgenic programs in development. However, even with state-of-the-art methods for generating transgenic founder (first generation) goats remain relatively inefficient and expensive. The production of transgenic animals by nuclear transfer can be hindered by placental and developmental abnormalities in the fetus. Studies in the mouse have indicated that tetraploid embryo complementation can be used to rescue embryos with lethal placental deficiencies and produce live offspring. We propose to establish the feasibility of tetraploid embryo complementation for cattle and goat embryos by: (1) creating tetraploid embryos from cattle and goat in vitro produced embryos, (2) combining tetraploid embryos with nuclear transfer embryos, and (3) track the tetraploid cells in the developing aggregate embryo. If this approach is successful, it could increase the number of transgenic animals produced from nuclear transfer.