MIDGESTATIONAL LETHALITY IN MICE LACKING KERATIN-8

Keratin 8 (mK8) and its partner keratin 18 (mK18) are the first interm ediate filament proteins expressed during mouse embryogenesis. They ar e found in most extraembryonic and embryonic simple epithelia, includi ng trophectoderm, visceral yolk sac, gastrointestinal tract, lungs, ma mmary glands, and uterus. We report that a targeted null mutation in t he mK8 gene causes mid-gestational lethality. Mutant embryos are growt h retarded and suffer from internal bleeding, with an abnormal accumul ation of erythrocytes in fetal livers. The mK8-phenotype has 94% penet rance, with a few mice surviving into adulthood. We suggest that mK8/m K18 filaments are important for the integrity of the fetal liver, like specialized human epidermal keratins for the integrity of the epiderm is. This phenotype in mice differs from the reported function of simpl e epithelium keratins in Xenopus at the gastrulation stage. In mice, m K8 fulfills a vital function at 12 days postcoitum.