Transcriptional repression and differential splicing of Fas mRNA by early transposon (ETn) insertion in autoimmune lpr mice.
Transcriptional repression and differential splicing of Fas mRNA by early transposon (ETn) insertion in autoimmune lpr mice.
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自身免疫 lpr 小鼠中早期转座子 (ETn) 插入对 Fas mRNA 的转录抑制和差异剪接。
DOI：
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
Toshimitsu Uede
中科院分区：
文献类型：
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作者：
Seiichi Kobayashi;Takeshi Hirano;Mitsuaki Kakinuma;Toshimitsu Uede
淋巴增殖(LPR)是由Fas基因突变导致的一种隐性性状，该突变使Fas转录本显著减少。当使用围绕Fas mRNA特定部分的一对引物进行逆转录聚合酶链式反应(RT-PCR)时，LPR胸腺细胞持续产生野生型和约180个碱基对(BP)长的PCR产物。后者插入183个核苷酸，与早期转座子(ETN)有98.9%的同源性，ETN位于小鼠浆细胞瘤P3.26Bu4的免疫球蛋白开关区域。这些数据清楚地表明，ETN插入Fas基因内含子会导致转录抑制。然而，这种缺陷可能是泄漏的，因为通过从Fas转录本中剪接出含有ETN的内含子，产生了完整的Fas mRNA。插入的183个碱基片段可能编码61个氨基酸，因此也可能产生突变的Fas抗原。野生型和突变型Fas抗原的低水平表达可能与LPR小鼠的变异表型有关。
Lpr (lymphoproliferation) is a recessive trait caused by a mutation in the Fas gene which reduces the Fas transcript substantially. When reverse transcription polymerase chain reaction (RT-PCR) was performed using pairs of primers surrounding a particular portion of Fas mRNA, wild-type and approximately 180 base pair (bp) longer PCR products were consistently generated from lpr thymocytes. The latter contained an insertion of 183 nucleotides which was 98.9% homologous to early transposon (ETn) which was found in an immunoglobulin switch region of murine plasmacytoma, P3.26Bu4. These data clearly indicate that ETn insertion into the Fas gene intron causes transcriptional repression. However, this defect may be leaky due to the production of intact Fas mRNA by splicing out ETn-containing intron from primary Fas transcripts. The inserted 183 bp fragment has a potential to code in-frame 61 amino acids, so that the mutant Fas antigen may also be produced. Low level expression of wild-type and mutant Fas antigens may be relevant to the variable phenotype in lpr mice.