Insertion of a retroviral solo long terminal repeat in mdr-3 locus disrupts mRNA splicing in mice
Insertion of a retroviral solo long terminal repeat in mdr-3 locus disrupts mRNA splicing in mice
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在 mdr-3 位点中插入逆转录病毒单独长末端重复序列会破坏小鼠的 mRNA 剪接
DOI：
10.1007/s003350010176
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发表时间：
2000
期刊：
影响因子：
2.5
通讯作者：
Hee
中科院分区：
文献类型：
--
作者：
K. Jun;Seong;Hee
先前，阿伯菌素诱导的CF-1小鼠亚群的神经毒性被证明是由缺乏mdr- 3p糖蛋白引起的。在这里，我们描述了CF-1小鼠亚群中themr -3基因突变的分子性质。伊维菌素敏感突变小鼠的mdr- 3mrna转录物大小与野生型小鼠不同。从突变脑中分离的RT-PCR产物序列分析显示，转录本中他们dr-3基因的23外显子被删除或改变。基因组位点分析显示，在themr -3基因的内含子中反向插入了一个单独的长末端重复序列（LTR），导致剪接异常，从而破坏了themr -3基因的功能。此外，对伊维菌素处理突变体的大脑进行的组织病理学分析显示，海马CA3区出现选择性神经元变性。这是首次报道的由单独逆转录病毒LTR诱导的基因突变在小鼠中具有表型后果的病例，并可能为理解病毒单独LTR序列对哺乳动物基因表达的影响提供新的见解。
Previously, the abermectin-induced neurotoxicity of subpopulation of CF-1 mice was shown to be caused by the deficiency ofmdr-3P-glycoprotein. Here, we have characterized the molecular nature of themdr-3gene mutation in this subpopulation of CF-1 mice. The size ofmdr-3mRNA transcript from ivermectin-sensitive mutant mice was different from that of wild-type mice. Sequence analysis of RT-PCR products isolated from the mutant brain disclosed that the exon 23 of themdr-3gene is deleted or altered in the transcripts. The analysis of the genomic locus revealed an insertion of a solo long terminal repeat (LTR) of the ecotropic murine leukemia virus in the reverse orientation in the intron of themdr-3gene, causing abnormal splicing and thereby disrupting themdr-3gene function. In addition, histopathological analysis of the brains of the ivermectin-treated mutants revealed selective neuronal degeneration in the hippocampal CA3 region. This is the first reported case of a gene mutation induced by a solo retroviral LTR with a phenotypic consequence in the mouse, and may provide new insights into the understanding of the effects of viral solo LTR sequences on mammalian gene expression.
DOI：
10.1073/pnas.90.5.1756
发表时间：
1993-03-01
影响因子：
11.1
作者：
ADACHI, M;WATANABEFUKUNAGA, R;NAGATA, S
通讯作者：
NAGATA, S