Combined action of fluorouracil and two mutant genes on limb development in the mouse

Publisher Website
Google Scholar
Abstract
The influence of a teratogen on the penetrance and expressivity of two mutant genes that affect limb development in mice was investigated. A low dose of the teratogen, 5‐fluorouracil, produced preaxially hyperphalangous hind feet in a large proportion of wild type fetuses when injected at ten days of development. A high dose increased the frequency of hyperphalangy, caused tibial hemimelia in many hyperphalangous fetuses, and produced cleft palate and vertebral deformities.The mutations, luxoid and luxate, are autosomal semidominant genes that induce preaxially polydactylous hind feet in heterozygotes and tibial hemimelia in homozygotes. Other pleiotropic effects of luxoid in homozygotes are polydactylous forefeet, kinked tails, agenesis of the patella, and infertility in males. In luxate homozygotes the forefeet, tail and patella are normal but the fabella medialis, a sesamoid bone of the knee, is absent.Wild type females were mated to heterozygous luxoid or luxate males and injected with the low dose of fluorouracil. Some of the treated offspring were allowed to be delivered and were subsequnently mated to determine their genotypes. Tibial hemimelia was found in some heterozygous luxoid and luxate offspring but not in wild type offspring, demonstrating a combined effect of gene and tertogen on limb development. The syndrome of fluorouracil‐induced hind limb defects in all heterozygous offspring resembled the syndrome normally found in untreated luxate homozygotes, and therefore, in luxoid heterozygotes the florouracil‐induced phenotype was atypical. Male infertility, polydactylous forefeet, kinked tails, cleft palate, and vertebral defects were not found in fluorouracil‐treated heterozygotes of either mutant.