Abstract
We used homologous recombination in embryonic stem cells to generate mice heterozygous for an aryl hydrocarbon nuclear translocator (ARNT) null mutation. These mice were intercrossed, but no live homozygousArnt−/− knockout mice were produced among 64 newborns. Homozygotes diein uterobetween 9.5 and 10.5 days of gestation. Abnormalities included neural tube closure defects, forebrain hypoplasia, delayed rotation of the embryo, placental hemorrhaging, and visceral arch abnormalities. However, the primary cause of lethality appears to be failure of the embryonic component of the placenta to vascularize and form the labyrinthine spongiotrophoblast. This may be related to ARNT's known role in hypoxic induction of angiogenesis. We found no defects in yolk sac circulation.
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