Bíla V, Kren V, Liska F
Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic.
Folia Biol (Praha). 2000;46(6):264-72.
The teratogenic effect of RA was found to be significantly influenced both by genetic background and by the genotype of malformation mutation Lx. The presence of the Lx mutation and BN genetic background strongly increases the teratogenic effect of RA. On the contrary, the SHR genetic background was shown to protect foetuses from RA teratogenic affliction. Recombinant inbred 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 Lx 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 oligodactyly in SHR/BN on forelimbs as compared to SHR/SHR (92.2% vs 11.5%). In +/Lx progeny, forelimbs were significantly more afflicted with oligodactyly in SHR/BN +/Lx in comparison with both SHR/SHR and SHR/BXH2 foetuses, which 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 number after RA treatment was connected with BN modifiers. The polymorphism of normal morphogenetic factors was shown to be responsible not only for Lx. phenotypic manifestation, but also for the variability in the response to RA teratogenic action.
研究发现，视黄酸（RA）的致畸作用受到遗传背景和畸形突变Lx基因型的显著影响。Lx突变的存在以及BN遗传背景会显著增强RA的致畸作用。相反，SHR遗传背景则显示出可保护胎儿免受RA致畸影响。重组近交系BXH2具有BN和SHR基因的特定组合，在给予RA后，它表现出与单独的BN遗传背景相同的胚胎致死效应。在没有Lx突变的情况下，RA对SHR/SHR或SHR/BN后代的后肢没有影响，而与SHR/SHR相比，SHR/BN前肢多指畸形的发生率显著更高（92.2%对11.5%）。在+/Lx后代中，与SHR/SHR和SHR/BXH2胎儿相比，SHR/BN +/Lx前肢多指畸形的情况明显更严重，这表明负责多指畸形的BN修饰基因没有传递给BXH2品系。相反，SHR/BXH2、+/Lx后代的后肢畸形最为严重（62%为多指和/或少指）。在纯合Lx/Lx后代中，给予RA后，SHR/BXH2前肢多指畸形更为普遍，而在BN/BN后代中，少指畸形最为常见。在后肢方面，RA治疗后趾数减少最多与BN修饰基因有关。正常形态发生因子的多态性不仅被证明与Lx的表型表现有关，还与对RA致畸作用反应的变异性有关。
