Rescue of embryonic lethality in hepatocyte growth factor/scatter factor knockout mice

While the targeted disruption of a gene is a powerful tool for investigatin g the physiological functions of that gene, disruption of a gene essential for embryogenesis leads to embryonic death. Rescue of the defect(s) causing embryonic death should promote survival, thus permitting further evaluatio n of the roles that the gene plays later in the developmental process. Disr uption of the gene for mouse hepatocyte growth factor/scatter factor (HGF/S F) leads to middle-stage embryonic lethality because of a defect in placent al development. Here we report that a single injection of HGF/SF at embryon ic day 9.5 (E9.5) into the amniotic cavity of HGF/SF-/- embryos rescued the placental defect and resulted in the survival of the embryos until term. H istological analysis suggested that HGF/SF is also required at the late sta ge of development for tissue organogenesis. Thus, injection of a secreted f actor can be a useful method to rescue the defects causing embryonic lethal ity. (C) 2000 Wiley-Liss, Inc.