Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3

Mice lacking suppressor of cytokine signaling 3 (SOCS3) exhibited embryonic Lethality with death occurring between days 11 and 13 of gestation. At thi s stage, SOCS3(-/-) embryos were slightly smaller than wild type but appear ed otherwise normal, and histological analysis failed to detect any anatomi cal abnormalities responsible for the lethal phenotype. Rather, in all SOCS 3(-/-) embryos examined, defects were evident in placental development that would account for their developmental arrest and death. The placental spon giotrophoblast layer was significantly reduced and accompanied by increased numbers of giant trophoblast cells. Delayed branching of the chorioallanto is was evident, and, although embryonic blood vessels were present in the l abyrinthine layer of SOCS3(-/-) placentas, the network of embryonic vessels and maternal sinuses was poorly developed. Yolk sac erythropoiesis was nor mal, and, although the SOCS3(-/-) fetal liver was small at day 12.5 of gest ation (E12.5), normal frequencies of erythroblasts and hematopoietic progen itor cells, including blast forming unit-erythroid (BFU-E} and, colony form ing unit-erythroid (CFU-E) were present at both E11.5 and E12.5. Colony for mation for both BFU-E and CFU-E from SOCS3-/- mice displayed wild-type quan titative responsiveness to erythropoietin (EPO), in the presence or absence of IL-3 or stem cell factor (SCF). These data suggest that SOCS3 is requir ed far placental development but dispensable for normal hematopoiesis in th e mouse embryo.