Houdebine Louis-Marie
J Soc Biol. 2009;203(4):323-8. doi: 10.1051/jbio/2009037. Epub 2010 Feb 1.
The first transgenic animals, mice, were obtained in 1980. The techniques of gene transfer had to be adapted to obtain transgenic animals with an acceptable yield in about fifteen species. When the yield is low (low rate of random integration and targeted integration via homologous recombination), genetic modifications must be achieved in intermediate cells able to participate to the development of chimeric transgenic animals (ES cells, EG cells, iPS obtained by the dedifferentiation of somatic cells) or in somatic cells used as nuclear donor to generate transgenic clones. Various tools make possible a marked increase of homologous recombination efficiency (meganucleases and ZFN), or a gene inactivation at the genome level (direct or conditional knock out) or at the mRNA level (interfering RNAs). Vectors allow a more reliable transgene expression. Genetically modified animals are used mainly to obtain information on biological functions and human diseases. Transgenic animals produce recombinant pharmaceutical proteins in milk and soon in egg white. Pig organs adapted to be tolerated by patients might be tested in humans in five years. The projects based on the use of transgenesis to improve animal production are presently few. Transgenic salmon with accelerated growth might be on the market when their possible escape in oceans will be controlled.
首批转基因动物小鼠于1980年培育成功。基因转移技术必须加以改进，以便在约15个物种中获得产量可观的转基因动物。当产量较低时（随机整合率和通过同源重组进行的靶向整合率低），必须在能够参与嵌合转基因动物发育的中间细胞（胚胎干细胞、胚胎生殖细胞、通过体细胞去分化获得的诱导多能干细胞）或用作核供体以产生转基因克隆的体细胞中实现基因修饰。各种工具使得同源重组效率显著提高（巨核酸酶和锌指核酸酶），或在基因组水平（直接或条件性敲除）或mRNA水平（干扰RNA）实现基因失活成为可能。载体使转基因表达更可靠。转基因动物主要用于获取有关生物学功能和人类疾病的信息。转基因动物在乳汁中，不久后还将在蛋清中生产重组药用蛋白。适配于患者耐受的猪器官可能在五年内用于人体试验。目前，利用转基因技术提高动物产量的项目较少。生长加速的转基因鲑鱼在其可能逃入海洋的情况得到控制后可能投放市场。
