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PMID: 2579397 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues.

Jaenisch R, Schnieke A, Harbers K

Abstract

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 in virus spread and viremia in all animals by 3 weeks of age. In contrast, infectious virus was not generated in F1 mice that had been treated during gestation with up to sublethal doses of the drug. Our results demonstrate that injection of 5-azacytidine can be used to efficiently and reproducibly activate silent genes in different cell populations of postnatal mice.

MeSH Terms
Age Factors Animals Azacitidine/pharmacology Cells, Cultured Gene Expression Regulation/drug effects Mice Retroviridae/genetics Transcription, Genetic/drug effects Virus Replication/drug effects
Chemicals
Azacitidine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Jaenisch R
Schnieke A
Harbers K
References (43)
43 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1985-03-00
Pages
1451-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC397280
Subset
IM
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