Transgenic Approaches to Study the Functions of the Transforming Growth Factor-β Superfamily Members

The tranforming growth factor-β (TGF-β)-related proteins belong to a large superfamily of secreted growth factors (1). New members of the family are still being discovered through homology-based techniques, and more than 25 mammalian members have been discovered (1–9). The in vivo functions of many of these new members are currently not known. Embryonic stem (ES) cell technology (10–12), a powerful genetic tool, has allowed the delineation of the essential function of some of these proteins and thus has opened up new avenues of research by uncovering unknown functions. With the increasing use of ES cell technology, many new mutant mouse strains have been generated and analyzed in which members of the TGF-β family, their receptors, or ligand-binding proteins have been rendered functionally inactive. This chapter focuses on those genes that have been recently “knocked out” (Table 22.1). As the signaling pathways for these proteins are studied in greater detail, the importance of this superfamily in reproduction, development, and oncogenesis will become increasingly clear.