Interactions between cycloheximide andT-locus alleles during mouse embryogenesis

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Abstract
Female CD‐1 mice were mated with CD‐1 × T/ + F1 males that were heterozygous for the brachyury (T) semidominant lethal gene or were +/+. Fetuses from CD‐1 × +/ + matings were normal when observed on gestation Day 17 (plug day = Day 0). Those from the CD‐1 × 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 × tw18/+ F1 males. Fetuses from the CD‐1 × tw18/+ matings were normal. CD‐1 females carrying CD‐1 X +/+, CD‐1 × T/+, or CD‐1 × 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 × T/ + or tw18/ + litters in comparison with CD‐1 × +‐/ + litters, as were nonvertebral skeletal defects in CD‐1 × 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 × tw18/ + litters. The incidence of taillessness was also higher in treated (26%) than in control (10%) CD‐1 × 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.