THE TERATOGENIC ACTION OF RETINOIC ACID IN RAT CONGENIC AND RECOMBINANT INBRED STRAINS

The teratogenic effect of all-trans retinoic acid (RA) was tested in t he system of congenic and recombinant inbred (RI) strains of the labor atory rat carrying the mutant Lx allele which determines the polydacty lyluxate syndrome. It was demonstrated that the teratogenic effect of RA is influenced by both the genotype at the Lx locus and the modifyin g genes. The dose of 100 mg/kg administered by gavage on day 11 of pre gnancy induced a statistically significant incidence of preaxial polyd actyly in hind limbs of LEW/BN, +/Lx foetuses heterozygous in the muta nt allele, whereas no specific limb defects were noted in foetuses LEW /BN, +/+ without the mutant allele, In foetuses homozygous in the muta nt allele LEW/BN, Lx/Lx and SHR/BXH2, Lx/Lx, RA conversely induced a s ignificant reduction in the number of toes on the preaxial side of hin d limbs and a reduction of the zeugopodium, mostly the tibia. Reductio n changes were more marked in SHR/BXH2, Lx/Lx foetuses, in which the t ibia was entirely missing and sirenomelia was found. The foetuses in t his group have in their genetic background a combination of modifiers that are responsible for oligodactyly and tibial hemimelia in the BXH2 strain. On the basis of continuing mapping of the rat genome, the tes ting of RA in the system of RI and congenic strains sill be utilized f or identification of so far hypothetical genes involved in morphogenes is.