Functional analysis of mammalian members of the transforming growth factor-beta superfamily.

ABSTRACT

Analysis of growth factor function has come from studies both in vitro and in vivo. However, the generation of mice deficient in a specific growth factor via gene targeting (for example, "knockout") strategies in embryonic stem (ES) cells will often evaluate the essential roles of the protein in vivo and, in many cases, discover new functions. In this review, studies to date are discussed on the generation and analysis of mice deficient in members of the transforming growth factor (TGF-beta) superfamily. Among the genes targeted via ES cell strategies are the TGF-beta1, Müllerian-inhibiting substance (MIS), inhibin alpha, activin betaA, and activin betaB genes. In addition, the mouse short ear and brachypodism mutants and insertional mutant 413-d have been identified as mutations in the BMP-5, GDF-5, and nodal loci, respectively. These studies have led to critical insights into the functions of these gene products and have further emphasized the importance of members of the TGF-beta superfamily in mammalian development, reproduction, and oncogenesis.