DEVELOPMENT OF CLONE TRANSGENIC RABBITS FOR THE STUDY OF ATHEROSCLEROSIS

转基因兔在许多生物医学领域被广泛用作生产治疗性蛋白的生物反应器和人类疾病模型。为了尝试利用核移植技术获得转基因兔，我们进行了利用转基因兔的体细胞克隆兔的初步试验，并对可能影响核移植成功的几个因素进行了优化，如培养液、融合和激活条件等相关因素。本研究采用电融合和压电法两种方法。尽管体细胞克隆兔还处于未成熟阶段，但与其他物种(山羊、绵羊、牛、小鼠和猪)相比，体细胞核移植克隆兔的过程相当复杂，需要经过许多步骤才能成功地克隆兔。在研究的第二部分，我们研究了表达人载脂蛋白(A)的转基因兔在胆固醇饮食喂养后脂蛋白(A)致动脉粥样硬化的情况。我们发现转基因兔的主动脉和冠状动脉比对照兔出现了更严重的动脉粥样硬化。

Transgenic rabbits are widely used as both bioreactors for the production of therapeutic proteins and human disease models in many biomedical fields. In attempt to generate transgenic rabbits by nuclear transfer technique, we performed the initial trial in making clone rabbits using somatic cells from transgenic rabbits and herewith we have optimized several factors that may be involved in the success of nuclear transfer procedures such as culture media, fusion and activation conditions and other related factors. Both electric fusion and piezo methods were used in this study. Although the generation of clone rabbits using somatic cells is still in immature state, it seems that compared to other species (goat, sheep, cow, mouse and pig), rabbit cloning using somatic cell nuclear transfer is rather complicated and a lot of procedures need to be refined before we can succeed in making cloned rabbits. In the second part of the study, we investigated transgenic rabbits expressing human apo(a) in terms of Lp(a) atherogenicity after cholesterol diet feeding. We found that transgenic rabbits developed greater atherosclerosis in aorta and coronary arteries than did control rabbits.