PMID: 2491005Jan 1, 1989Paper

The significance of genetic factors for thalidomide teratogenicity in the Norway rat

Acta Universitatis Carolinae. Medica
V Bila, V Kren

Abstract

Thalidomide teratogenicity was tested on a model based on the system of congenic strains of the laboratory rat, including the mutant allele lx, which determines the polydactyly-luxate syndrome. The phenotypic expression of the allele lx changes according to the genetic background of the carrier and also according to factors of the external environment. On a hybrid genetic background LEW/BN the allele lx acts as recessive, and heterozygotes +/lx are unaffected. In a number of experiments it was proved, however, that these hybrids (LEW/BN, +/lx) had an increased sensitivity to the induction of limb malformations (polydactyly, tibial hemimelia, oligodactyly) by various teratogens. Thalidomide was administered on the 12th day of pregnancy by the intraperitoneal route in a mixture of Tween 20 with saline (1:3) in doses of 25, 50 and 200 mg/kg to females with genetic background LEW that were purposely mated with males of the BN or BN.lx strains. The produced progeny had genotypes LEW/BN, +/+ or LEW/BN, +/lx. In offsprings that had in the genotype the mutant allele lx in a heterozygous condition (+/lx) preaxial polydactyly of hind limbs developed after all the thalidomide doses tested. This malformation occurred in 17 out of 18 litter...Continue Reading

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