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The transgenic rabbits containing a human apoA-i antisense gene as a model for genetic correction of atherogenic disturbances of lipid metabolism
1Perevozchikov A. P., 1Valsman B. L., 1Dozortsev D. I., 1Sorokin A. V., 1Orlov S. V., 1Denisenko A. D., 1Dyban A. P., 1Klimov A. N.
  1. Institute of Experimental Medicine, Academy of Medical Sciences of the USSR
    Leningrad, USSR


The recombinant DNA molecules containing potentially expressing human apoA-I antisence gene were constructed and injected into the rabbit zygotes. Dot-blot hybridization techniques as well as lipid and lipoprotein analyses methods were used to reveal transgenic animals. It was found that DNAs of several rabbits contained up to 40 copies of molecules of foreign DNA per genome. It was interesting that the patterns of serum lipid and lipoprotein metabolism of transgenic animals were shifted to atherogenic phenotype. In one case the expression of the antisense gene was able to suppress the synthesis of high-density lipoproteins. In two other cases the expression of this gene as appeared was correlated with a decrease of α-lipoprotein cholesterol level. In all the cases serum cholesterol and (or) triglyceride levels increased as well. Thus, the obtained transgenic rabbits may serve as a model to study and genetically correct atherogenic disturbances of lipid metabolism.


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