Robert Valérie J, Bessereau Jean-Louis
Ecole Normale Supérieure, Biologie Cellulaire de Synapse, Inserm, U789, 75005 Paris, France.
Genetica. 2010 May;138(5):541-9. doi: 10.1007/s10709-009-9362-2. Epub 2009 Apr 5.
Tc1, one of the founding members of the Tc1/mariner transposon superfamily, was identified in the nematode Caenorhabditis elegans more than 25 years ago. Over the years, Tc1 and other endogenous mariner transposons became valuable tools for mutagenesis and targeted gene inactivation in C. elegans. However, transposition is naturally repressed in the C. elegans germline by an RNAi-like mechanism, necessitating the use of mutant strains in which transposition was globally derepressed, which causes drawbacks such as uncontrolled proliferation of the transposons in the genome and accumulation of background mutations. The more recent mobilization of the Drosophila mariner transposon Mos1 in the C. elegans germline circumvented the problems inherent to endogenous transposons. Mos1 transposition strictly depends on the expression of the Mos transposase, which can be controlled in the germline using inducible promoters. First, Mos1 can be used for insertional mutagenesis. The mobilization of Mos1 copies present on an extrachromosomal array results in the generation of a small number of Mos1 genomic insertions that can be rapidly cloned by inverse PCR. Second, Mos1 insertions can be used for genome engineering. Triggering the excision of a genomic Mos1 insertion causes a chromosomal break, which can be repaired by transgene-instructed gene conversion. This process is used to introduce specific changes in a given gene, such as point mutations, deletions or insertions of a tag, and to create single-copy transgenes.
Tc1是Tc1/水手转座子超家族的创始成员之一,25多年前在秀丽隐杆线虫中被发现。多年来,Tc1和其他内源性水手转座子成为秀丽隐杆线虫诱变和靶向基因失活的重要工具。然而,在秀丽隐杆线虫生殖系中,转座通过一种类似RNA干扰的机制被自然抑制,这就需要使用转座在整体上不受抑制的突变株,但这会带来一些缺点,比如转座子在基因组中不受控制地增殖以及背景突变的积累。最近,果蝇水手转座子Mos1在秀丽隐杆线虫生殖系中的移动规避了内源性转座子固有的问题。Mos1转座严格依赖于Mos转座酶的表达,而Mos转座酶可以在生殖系中使用可诱导启动子进行控制。首先,Mos1可用于插入诱变。位于染色体外阵列上的Mos1拷贝的移动会产生少量可通过反向PCR快速克隆的Mos1基因组插入。其次,Mos1插入可用于基因组工程。触发基因组中Mos1插入的切除会导致染色体断裂,这种断裂可通过转基因指导的基因转换进行修复。这个过程用于在给定基因中引入特定变化,如点突变、标签的缺失或插入,并创建单拷贝转基因。