Bílá V, Kren V
Department of Biology, 1st Medical Faculty, Charles University, Prague, Czech Republic.
Folia Biol (Praha). 1996;42(4):167-73.
The teratogenic effect of all-trans retinoic acid (RA) was tested in the system of congenic and recombinant inbred (RI) strains of the laboratory rat carrying the mutant Lx allele which determines the polydactyly-luxate syndrome. It was demonstrated that the teratogenic effect of RA is influenced by both the genotype at the Lx locus and the modifying genes. The dose of 100 mg/kg administered by gavage on day 11 of pregnancy induced a statistically significant incidence of preaxial polydactyly in hind limbs of LEW/BN, +/Lx foetuses heterozygous in the mutant allele, whereas no specific limb defects were noted in foetuses LEW/BN, +/+ without the mutant allele. In foetuses homozygous in the mutant allele LEW/BN, Lx/Lx and SHR/BXH2, Lx/Lx, RA conversely induced a significant reduction in the number of toes on the preaxial side of hind limbs and a reduction of the zeugopodium, mostly the tibia. Reduction changes were more marked in SHR/BXH2, Lx/Lx foetuses, in which the tibia was entirely missing and sirenomelia was found. The foetuses in this 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 testing of RA in the system of RI and congenic strains will be utilized for identification of so far hypothetical genes involved in morphogenesis.
在携带决定多指-关节脱位综合征的突变Lx等位基因的近交系和重组近交（RI）系实验大鼠系统中，测试了全反式维甲酸（RA）的致畸作用。结果表明，RA的致畸作用受Lx位点的基因型和修饰基因的影响。在妊娠第11天经口灌胃给予100mg/kg的剂量，在携带突变等位基因的杂合子LEW/BN，+/Lx胎儿的后肢中诱导出统计学上显著的轴前多指发生率，而在没有突变等位基因的LEW/BN，+/+胎儿中未发现特定的肢体缺陷。在突变等位基因纯合的LEW/BN，Lx/Lx和SHR/BXH2，Lx/Lx胎儿中，RA反而导致后肢轴前侧脚趾数量显著减少以及小腿（主要是胫骨）缩短。在SHR/BXH2，Lx/Lx胎儿中减少变化更为明显，其中胫骨完全缺失并发现并腿畸形。该组胎儿在其遗传背景中具有负责BXH2品系少指和胫骨半肢畸形的修饰基因组合。基于大鼠基因组的持续定位，RI系和近交系系统中RA的测试将用于鉴定迄今为止参与形态发生的假设基因。
