We have isolated a novel mouse gene (Gtl2) from the site of a gene trap integration (Gtl2lacZ) that gave rise to developmentally regulated lacZ expression, and a dominant parental‐origin–dependent phenotype. Heterozygous Gtl2lacZ mice that inherited the transgene from the father showed a proportionate dwarfism phenotype, whereas the penetrance and expressivity of the phenotype was strongly reduced in Gtl2lacZ mice that inherited the transgene from the mother. Gtl2 expression is highly similar to the β‐galactosidase staining pattern, and is down‐regulated but not abolished in mice carrying the Gtl2lacZ insertion. In early postimplantation embryos, Gtl2 is expressed in the visceral yolk sac and embryonic ectoderm. During subsequent development and organogenesis, Gtl2 transcripts are abundant in the paraxial mesoderm closely correlated with myogenic differentiation, in parts of the central nervous system, and in the epithelial ducts of developing excretory organs. The Gtl2 gene gives rise to various differentially spliced transcripts, which contain multiple small open reading frames (ORF). However, none of the ATG codons of these ORFs is in the context of a strong Kozak consensus sequence for initiation of translation, suggesting that Gtl2 might function as an RNA. Nuclear Gtl2 RNA was detected in a temporally and spatially regulated manner, and partially processed Gtl2 transcripts were readily detected in Northern blot hybridizations of polyadenylated RNA, suggesting that primary Gtl2 transcripts are differently processed in various cell types during development. Gtl2 transcript levels are present in parthenogenic embryos but may be reduced, consistent with the pattern of inheritance of the Gtl2lacZ phenotype. Dev. Dyn. 1998;212:214–228. © 1998 Wiley‐Liss, Inc.

In eutherian mammals, implantation and establishment of the chorioallantoic placenta are essential for embryo development and survival. As a maternal response to implantation, uterine stromal cells proliferate, differentiate, and generate the decidua, which encapsulates the conceptus and forms the maternal part of the placenta. Little is known about decidual functions and the molecular interactions that regulate its development and maintenance. Here we show that the receptor for the cytokine interleukin-11 (IL-11R␣) is required specifically for normal establishment of the decidua. Females homozygous for a hypomorphic IL-11R␣ allele are fertile and their blastocysts implant and elicit the decidual response. Because of reduced cell proliferation, however, only small deciduae form. Mutant deciduae degenerate progressively, and consequently embryo-derived trophoblast cells generate a network of trophoblast giant cells but fail to form a chorioallantoic placenta, indicating that the decidua is essential for normal fetoplacentation. IL-11R␣ is expressed in the decidua as well as in numerous other tissues and cell types, including the ovary and lymphocytes. The differentiation state and proliferative responses of B and T-lymphocytes in mutant females were normal, and wild-type females carrying IL-11R␣ mutant ovaries had normal deciduae, suggesting that the decidualization defects do not arise secondarily as a consequence of perturbed IL-11R␣ signaling defects in lymphoid organs or in the ovary. Therefore, IL-11R␣ signaling at the implantation site appears to be required for decidua development.

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Interleukin-11 (IL-11) is a multifunctional cytokine involved in the regulation of cell proliferation and differentiation in a variety of cell types and tissues in vitro and in vivo. The effects of IL-11 were shown to be mediated by the IL-11 receptor (hereafter referred to as IL-11 R alpha), which is a ligand-binding subunit and provides ligand specificity in a functional multimeric signal-transduction complex with gp130. Here we show that the mouse genome contains a second gene encoding an IL-11-binding protein, referred to as IL-11R beta. The structure of the IL-11R beta gene is highly similar to that of IL-11R alpha, and IL-11R beta exhibits 99% sequence identity with IL-11R alpha at the amino acid level. IL-11R beta is co-expressed with IL-11R alpha, albeit at lower levels, in embryos and in various adult tissues. IL-11R beta transcripts are abundant in testis, and, in contrast with IL-11R alpha, absent from skeletal muscle. IL-11R beta expressed in vitro binds IL-11 with high affinity, suggesting that the mouse genome contains a second functional IL-11R.