Interactions between cycloheximide and T-locus alleles during mouse embryogenesis

Female CD-1 mice were mated with CD-1 X T/ + F1 males that were heterozygous for the brachyury (T') semidominant lethal gene or were +/+. Fetuses from CD-1 X +/+ matings were normal when observed on gestation Day 17 (plug day = Day 0). Those from the CD-1 X T/+ cross exhibited the expected 1:1 ratio of short:normal tail lengths, but 10% of these fetuses were tailless, apparently due to factors in the CD-1 genotype that increased the expressivity of the T-gene with regard to reduction of tail length. Additional CD-1 females were mated with CD-1 X tw18/+ F1 males. Fetuses from the CD-1 X tw18/+ matings were normal. CD-1 females carrying CD-1 X +/+, CD-1 X T/+, or CD-1 X tw18/+ litters were injected ip on gestation Day 9 with 30 mg/kg cycloheximide or were untreated. Cycloheximide was teratogenic for litters from all three crosses. Polydactyly, oligodactyly, and a variety of skeletal abnormalities were observed. Gross malformations and total skeletal malformations were increased in treated CD-1 X T/ + or tw18/+ litters in comparison with CD-1 X +/+ litters, as were nonvertebral skeletal defects in CD-1 X tw18/+ litters. Prenatal mortality was also greater in treated mutant-containing litters than in +/+ litters, and fetal weights were similarly decreased in treated CD-1 X tw18/+ litters. The incidence of taillessness was also higher in treated (26%) than in control (10%) CD-1 X T/+ litters. Thus both the T and tw18 alleles appear to have enhanced the teratogenicity of cycloheximide, and the inhibitor may have increased the expressivity of T.