Developmental studies of the lethal gene Bld in the mouse. I. Post-implantation development of the lethal homozygote.

In matings of Bld/+ x Bld/+ mice a characteristic type of abnormal embryo is found on days 6 and 7 after impregnation which dies at 8 days and accounts for about 25% of all living embryos. These embryos are regarded as the fethal Bld/Bld homozygotes. Before 6 days the embryos appear slightly retarded. Entodermal cells invade the yolk sac and the trophectoderm does not fuse to the uterine decidua. Late on day 6 the yolk sac is filled with a cap of unorganized cells of entodermal origin, surrounded by both a thick membrane of non-living material, corresponding to Reichert's membrane, and external to this a continuous layer of trophectoderm: there is still almost no contact with uterine tissue. At 7 days 10 h amniotic folds are formed. Mesoderm appears occasionally but is not always present; when it appears it does not grow out from its place of origin. Entodermal cells, particularly in the proximal part of the extra-embryonic region, become polyploid. At the same time, the trophectoderm makes contact with the uterine decidua and gives rise to primary giant cells. Twelve hours later, the embryonic cells begin to degenerate, first in the region of the amniotic fold and the mesoderm. The embryo dies shortly afterwards. It is suggested that the primary target tissues affected by the Bld/Bld constitution are trophectoderm and entoderm. Many but not all of the abnormal features appearing later can by ascribed to insufficient nutrition of the embryo, due to failure of attachment of the trophectoderm and the filling of the yolk sac with entodermal cells.