ABSTRACTgpl30 is a ubiquitously expressed signaltransducing receptor component shared by interleukin 6, interleukin 11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1. To investigate physiological roles of gpl30 and to examine pathological consequences of a lack of gpl30, mice deficient for gpl30 have been prepared. Embryos homozygous for the gpl30 mutation progressively die between 12.5 days postcoitum and term. On 16.5 days postcoitum and later, they show hypoplastic ventricular myocardium without septal and trabecular defect. Cytokine signals are mediated through specific receptor complexes, whose components belong, in most cases, to a large group of proteins called the cytokine receptor family (1). These receptor complexes are usually composed of a ligandspecific receptor chain and a signal transducer common to multiple cytokines. gp130 was initially identified as a signal transducing receptor component that associates with the interleukin 6 receptor (IL-6R) when the receptor binds interleukin 6 (IL-6) (2). gp130 is also utilized as a critical signaling component in the receptor complexes for interleukin 11, leukemia inhibitory factor (LIF), oncostatin M, ciliary neurotrophic factor (CNTF), and cardiotrophin 1 (CT-1) (refs. 1 and 3 and references therein). The discovery of this shared signal transducer, gpI30, helps to explain how these different cytokines mediate overlapping biological functions. IL-6 binding to IL-6R induces homodimerization of gp130 (4), whereas stimulation by LIF, CNTF, oncostatin M, and CT-1 leads to heterodimerization of gpl 30 with a closely related protein, LIF receptor (3, 5). Homo-or heterodimerization of gpl30 triggers the activation of JAKI, JAK2, and TYK2, members of the JAK family of cytoplasmic tyrosine kinases that are associated with gpl30 (6-8). This leads to subsequent tyrosine phosphorylation and functional activation of a latent cytoplasmic transcription factor,