TREATMENT OF MICE WITH 5-AZACYTIDINE EFFICIENTLY ACTIVATES SILENT RETROVIRAL GENOMES IN DIFFERENT TISSUES
TREATMENT OF MICE WITH 5-AZACYTIDINE EFFICIENTLY ACTIVATES SILENT RETROVIRAL GENOMES IN DIFFERENT TISSUES
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DOI：
10.1073/pnas.82.5.1451
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
HARBERS, K
中科院分区：
文献类型：
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作者：
JAENISCH, R;SCHNIEKE, A;HARBERS, K
将药物 5-氮杂胞苷注射到小鼠体内以激活沉默的逆转录病毒基因组。使用了 Mov-7 和 Mov-10 小鼠亚系，每种小鼠都携带莫洛尼鼠白血病原病毒，其编码区的突变位置不相同。这些原病毒基因组高度甲基化，在动物中不表达。治疗后 3 天，将药物单次注射到出生后的小鼠体内，即可诱导胸腺、脾脏和肝脏中内源性缺陷前病毒基因组的转录。在暴露于药物的动物的大脑中没有检测到病毒转录。当出生后的 Mov-7/Mov-10 F1 小鼠接受该药物治疗时，感染性病毒有效产生，并导致所有动物在 3 周龄时出现病毒传播和病毒血症。在妊娠期间接受亚致死剂量药物治疗的 F1 小鼠中没有产生传染性病毒。注射 5-氮杂胞苷可用于有效且可重复地激活出生后小鼠不同细胞群中的沉默基因。
The drug 5-azacytidine was injected into mice to activate silent retroviral genomes. The Mov-7 and Mov-10 substrains of mice were used, each of which carries a Moloney murine leukemia provirus with mutations in the coding regions at nonidentical positions. These proviral genomes are highly methylated and are not expressed in the animal. A single injection of the drug into postnatal mice induced transcription of the endogenous defective proviral genomes in thymus, spleen and liver at 3 days after treatment. No viral transcription was detected in the brain of drug-exposed animals. When postnatal Mov-7/Mov-10 F1 mice were treated with the drug, infectious virus was generated efficiently and resulted into virus spread and viremia in all animals by 3 wk of age. Infectious virus was not generated in F1 mice that was treated during gestation with up to sublethal doses of the drug. Injection of 5-azacytidine can be used to efficiently and reproducibly activate silent genes in different cell populations of postnatal mice.