ABERRANT TRANSCRIPTION CAUSED BY THE INSERTION OF AN EARLY TRANSPOSABLE ELEMENT IN AN INTRON OF THE FAS ANTIGEN GENE OF LPR MICE
ABERRANT TRANSCRIPTION CAUSED BY THE INSERTION OF AN EARLY TRANSPOSABLE ELEMENT IN AN INTRON OF THE FAS ANTIGEN GENE OF LPR MICE
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DOI：
10.1073/pnas.90.5.1756
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发表时间：
1993-03-01
影响因子：
11.1
通讯作者：
NAGATA, S
中科院分区：
文献类型：
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作者：
ADACHI, M;WATANABEFUKUNAGA, R;NAGATA, S
小鼠lpr（淋巴细胞增殖）突变携带Fas抗原染色体基因重排，介导细胞凋亡。对野生型和lpr小鼠Fas抗原染色体基因的分离和鉴定表明，lpr小鼠Fas抗原基因的内含子2中插入了一个早期转座元件（ETn）。携带Fas抗原和ETn序列的杂交转录本在突变体的胸腺和肝脏中表达。这表明，由ETn插入内含子引起的Fas抗原转录物的过早终止和异常剪接是突变小鼠淋巴细胞增殖和自身免疫表型的原因。另一方面，将ETn插入哺乳动物表达载体的内含子中会显著但不完全降低表达效率。这些发现表明lpr小鼠能够表达非常低水平的Fas抗原。
The mouse lpr (lymphoproliferation) mutation carries a rearrangement in the chromosomal gene for the Fas antigen, which mediates apoptosis. Isolation and characterization of mouse Fas antigen chromosomal gene from wild-type and lpr mice indicated an insertion of an early transposable element (ETn) in intron 2 of the Fas antigen gene of lpr mice. Hybrid transcripts carrying the Fas antigen and ETn sequences were expressed in the thymus and liver of the mutant. This indicated that premature termination and aberrant splicing of the Fas antigen transcript caused by the insertion of the ETn in the intron are responsible for the lymphoproliferation and autoimmune phenotype of the mutant mouse. On the other hand, an insertion of the ETn into an intron of a mammalian expression vector dramatically but not completely reduced the expression efficiency. These findings suggest that lpr mice are able to express a very low level of the Fas antigen.