首页> 外文期刊>Journal of biochemical and molecular toxicology >The subpopulation of CF-1 mice deficient in P-glycoprotein contains a murine retroviral insertion in the mdr1a gene.
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The subpopulation of CF-1 mice deficient in P-glycoprotein contains a murine retroviral insertion in the mdr1a gene.

机译:缺乏P-糖蛋白的CF-1小鼠亚群在mdr1a基因中包含鼠逆转录病毒插入。

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摘要

A subpopulation of the CF-1 mouse strain is sensitive to neurotoxicity following exposure to avermectins, a family of structurally related antiparasitic agents. This unusual sensitivity is the result of a deficiency in the mdr1a P-glycoprotein that normally contributes to a functional blood-brain barrier. Previous studies demonstrated a correlation between P-glycoprotein levels in the brain, intestine, testis, and placenta with an restriction fragment length polymorphism (RFLP) pattern from DNA isolated from the animals. We have demonstrated that only P-glycoprotein derived from the mdr1a gene is deficient in these mice. In this article, we describe the genetic defect in the subpopulation of CF-1 mice resulting in an absence of P-glycoprotein. The data presented describes a reverse transcription--polymerase chain reaction (RT-PCR) protocol that specifically amplifies mdr1a mRNA from tissue and confirms that the P-glycoprotein defect results from a truncated mRNA with a deleted exon 23. Genomic amplification and sequencing of the intron between exon 22 and 23 in Pgp-deficient animals reveals an insertion of approximately 8.35 kb of DNA at the exon 23 intron--exon junction corresponding to a murine leukemia virus. This insertion results in the aberrant splicing of the mRNA and the loss of exon 23 during RNA processing. Copyright 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:83-89, 2001
机译:CF-1小鼠品系的亚群在暴露于阿维菌素(一种结构相关的抗寄生虫剂家族)后对神经毒性敏感。这种异常的敏感性是通常导致功能性血脑屏障的mdr1a P-糖蛋白缺乏的结果。先前的研究表明,脑,肠,睾丸和胎盘中P糖蛋白水平与从动物体内分离的DNA的限制性片段长度多态性(RFLP)模式相关。我们已经证明只有mdr1a基因衍生的P糖蛋白在这些小鼠中是不足的。在本文中,我们描述了CF-1小鼠亚群中的遗传缺陷,导致缺乏P-糖蛋白。呈现的数据描述了一种逆转录聚合酶链反应(RT-PCR)方案,该方案可特异性扩增组织中的mdr1a mRNA,并证实P-糖蛋白缺陷是由带有缺失的外显子23的截短的mRNA引起的。缺乏Pgp的动物中第22外显子和第23外显子之间的内含子显示在对应于鼠类白血病病毒的第23外显子内含子-外显子连接处插入了约8.35 kb的DNA。这种插入导致在RNA加工过程中mRNA的异常剪接和外显子23的丢失。版权所有2001 John Wiley&Sons,Inc. J Biochem Mol Toxicol 15:83-89,2001

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