Andersson K B, Skålhegg B S
Universitetet i Oslo, Biokjemisk Institutt.
Tidsskr Nor Laegeforen. 1998 Oct 20;118(25):3952-7.
Genetic modification of mice by homologous recombination has rapidly become a central tool within molecular medicine and molecular biology. The use of such techniques allows precise mutation of single genes and study of the direct consequences in intact animals. A decade has passed since the a series of landmark studies demonstrated the feasibility of genetically modifying embryonic stem cells in mice by homologous recombination. This initiated the whole field of gene targeting, or "knockout" technology in mice. This article reviews briefly the historical and technical development of knockout technology, and the application to selected mouse models within cancer biology, immunology and neurobiology. Refinements of this type of genetic modification, with tissue- or time-specific genetic ablation or mutations, represent the next step in technology development. The combined use of Cre/loxP and homologous recombination has opened for a wide spectrum of possibilities, reaching far beyond null mutations. The rapid evolvement of the whole field has opened for genetic engineering--in the presise sense of the word--in whole animals.
通过同源重组对小鼠进行基因改造已迅速成为分子医学和分子生物学的核心工具。使用此类技术可实现单个基因的精确突变,并研究其在完整动物体内产生的直接后果。自一系列具有里程碑意义的研究证明通过同源重组对小鼠胚胎干细胞进行基因改造的可行性以来,已经过去了十年。这开启了小鼠基因靶向或“基因敲除”技术的整个领域。本文简要回顾了基因敲除技术的历史和技术发展,以及该技术在癌症生物学、免疫学和神经生物学中选定小鼠模型的应用。这种基因改造类型的改进,即组织或时间特异性基因消融或突变,代表了技术发展的下一步。Cre/loxP与同源重组的联合使用开启了广泛的可能性,远远超出了无效突变的范畴。整个领域的快速发展开启了对完整动物进行真正意义上的基因工程的大门。