CRE-MEDIATED SITE-SPECIFIC TRANSLOCATION BETWEEN NONHOMOLOGOUS MOUSE CHROMOSOMES

CRE-MEDIATED SITE-SPECIFIC TRANSLOCATION BETWEEN NONHOMOLOGOUS MOUSE CHROMOSOMES
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DOI:
10.1073/pnas.92.16.7376
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发表时间:
1995-08-01
影响因子:
11.1
通讯作者:
GROSVELD, G
GROSVELD, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
VANDEURSEN, J;FORNEROD, M;GROSVELD, G

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染色体重排,如易位的大缺失、倒位,介导染色体内或染色体之间大DNA片段的迁移,这可能对细胞遗传控制产生重大影响。一种染色体操作的方法对于研究哺乳动物细胞或动物中大规模DNA重排的后果是非常有用的。我们利用噬菌体P1的Cre-loxP重组系统,诱导小鼠胚胎干细胞13号染色体上的Dek基因和2号染色体上的Can基因位点特异性易位。据估计,在表达Cre重组酶的1200-2400个胚胎干细胞中,Cre介导的非同源小鼠染色体间易位的频率约为1。这些结果证明了在哺乳动物细胞中进行染色体操作的位点特异性重组系统的可行性,为染色体工程开辟了道路。
Chromosome rearrangements, such as large deletions, inversions, of 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.