Enhanced susceptibility of mouse embryos heterozygous for oligosyndactyly (Os/+) to mitomycin C-induced skeletal abnormalities.

The mouse mutation, oligosyndactyly (Os), results in syndactyly, muscle anomalies, and deficiency of nephrons in heterozygous animals and early embryonic lethality in homozygotes. Since the homozygous lethality results from mitotic arrest with intact spindles at the time of implantation, we have hypothesized that the heterozygous manifestations may result from impairment of cell proliferation in regions with high proliferative rates. To test this hypothesis, Os/+ and +/+ mouse embryos at 6.5 days of gestation were exposed to mitomycin C (MMC), an agent that causes a high degree of embryonic cell death which is "compensated" for by a period of rapid cell proliferation. 17.9% of MMC-treated +/+ fetuses had fused vertebrae, a significant increase over untreated fetuses, and this frequency was further increased to 33.6% in MMC-treated Os/+ fetuses. Saline treated Os/+ and +/+ fetuses showed the same low rate (0-3%) of vertebral fusion. These results indicate that Os/+ embryos have an increased sensitivity to the vertebral fusion-inducing effect of MMC at 6.5 days of gestation, a finding compatible with the hypothesis that rapid cell proliferation may be impaired in Os/+ embryos and fetuses.