The influence of the genetic background on the interaction of retinoic acid with Lx mutation of the rat

The teratogenic effect of RA was found to be significantly influenced both by genetic background and by the genotype of malformation mutation Lr, The presence of the Lr mutation and BN genetic background strongly increases th e teratogenic effect of RA. On the contrary, the SMR genetic background was shown to protect foetuses from RA teratogenic affliction. Recombinant inbr ed strain BXH2 is endowed with a specific combination of BN and SHR genes, and following RA administration it exhibits the same embryolethal effect as the BN genetic background alone. Without the IX mutation there was no effect of RA on hind limbs in SHR/SHR or SHR/BN progeny whilst there was a significantly higher occurence of olig odactyly in SHR/BN on forelimbs as compared to SHR/SHR (92.2% vs 11,5%), In +/Lx progeny, forelimbs were significantly more afflicted with oligodactyl y in SHR/BN +/Lx in comparison with both SHR/SHR and SHR/BXH2 foetuses, whi ch indicates that BN modifiers responsible for oligodactyly were not passed to the BXH2 strain. On the contrary, hind limbs of SHR/BXH2, +/Lx progeny exhibited the highest affliction (62% of polydactyly and/or oligodactyly). In homozygous Lx/Lx progeny, polydactyly prevailed in forelimbs of SHR/BXH2 following RA administration, whilst in BN/BN progeny oligodactyly was the most frequent affliction. On the hind limbs, the highest reduction of toe n umber after RA treatment was connected with BN modifiers. The polymorphism of normal morphogenetic factors was shown to be responsibl e not only for Lr phenotypic manifestation, but also for the variability in the response to RA teratogenic action.