Van Deursen J, Fornerod M, Van Rees B, Grosveld G
Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7376-80. doi: 10.1073/pnas.92.16.7376.
Chromosome rearrangements, such as large deletions, inversions, or translocations, mediate migration of large DNA segments within or between chromosomes, which can have major effects on cellular genetic control. A method for chromosome manipulation would be very useful for studying the consequences of large-scale DNA rearrangements in mammalian cells or animals. With the use of the Cre-loxP recombination system of bacteriophage P1, we induced a site-specific translocation between the Dek gene on chromosome 13 and the Can gene on chromosome 2 in mouse embryonic stem cells. The estimated frequency of Cre-mediated translocation between the nonhomologous mouse chromosomes is approximately 1 in 1200-2400 embryonic stem cells expressing Cre recombinase. These results demonstrate the feasibility of site-specific recombination systems for chromosome manipulation in mammalian cells in vivo, breaking ground for chromosome engineering.
染色体重排，如大片段缺失、倒位或易位，介导了染色体内部或染色体之间大片段DNA的迁移，这可能对细胞遗传控制产生重大影响。一种染色体操作方法对于研究哺乳动物细胞或动物中大规模DNA重排的后果将非常有用。利用噬菌体P1的Cre-loxP重组系统，我们在小鼠胚胎干细胞中诱导了13号染色体上的Dek基因与2号染色体上的Can基因之间的位点特异性易位。在表达Cre重组酶的非同源小鼠染色体之间，Cre介导的易位估计频率约为每1200 - 2400个胚胎干细胞中有1个。这些结果证明了位点特异性重组系统在体内对哺乳动物细胞进行染色体操作的可行性，为染色体工程开辟了道路。
