highly skilled investigators with extensive experience in gene targeting and mouse genetics describe their best techniques for the design of targeting constructs and for the analysis of the mouse phenotype. these include embryo transplantation, in vitro embryonic stem cell differentiation, creation of aggregation chimeras, mouse pathology, embryo cryopreservation, and transplantation. state-of-the-art and highly practical, gene knockout protocols not only constitutes an invaluable source of readily reproducible techniques for those just entering the field of gene targeting, but also a key reference for all genetic researchers today.