In vitro studies of mouse embryos bearing mutations at the T locus: tw5 and t12

Lethal mutations in the T region of chromosome 17 in the mouse cause death at specific stages of embryonic development. It is widely believed that death of homozygous mutant embryos occurs as a result of aberrant cell-cell interaction followed by disorganization and death of specific cell types within the embryo. In vitro culture of blastocysts homozygous for one of these mutations, tw5, has revealed that this mutation is lethal for all cells of the mutant embryo. In addition, measurements of beta-glucuronidase activity indicate that the lethal period of the tw5 mutation is the same in vitro as it is in vivo. Similar biochemical studies with t12 mutant embryos demonstrate that cessation of macromolecular synthesis occurs rather abruptly at the morula stage, the time at which those mutant embryos die in vivo. These results lead us to propose that all cells within the conceptus are directly and profoundly affected by early acting t mutations, and that failure of some cell types to organize properly is not an adequate explanation of the death of these mutants.