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Herpes simplex virus transcriptional activator VP16 is detrimental to preimplantation development in mice
Author(s) -
Yueh Y. Gloria,
Yaworsky Paul J.,
Kappen Claudia
Publication year - 2000
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/(sici)1098-2795(200001)55:1<37::aid-mrd6>3.0.co;2-n
Subject(s) - biology , transgene , transactivation , gene expression , blastocyst , herpes simplex virus , microbiology and biotechnology , gene , regulation of gene expression , enhancer , reporter gene , embryo , virology , virus , genetics , embryogenesis
The herpes simplex virus transactivator protein VP16 is frequently used to regulate gene expression in several experimental systems, including transgenic mice. It has been suggested that high levels of VP16 expression in mice may be lethal. In order to systematically address this issue, we linked the VP16 gene to promoters that are active early and in a variety of tissues throughout development, such as the human β‐actin promoter or the rat nestin gene enhancer. VP16 expression was assayed using a LacZ reporter gene linked to a VP16‐responsive immediate early gene promoter. We show here that expression of VP16 at high levels is detrimental to pre‐implantation development. By culturing embryos in vitro, we demonstrate that this effect is exerted at the transition from the 2‐cell to the 4‐cell stage, reducing survival to the blastocyst stage dramatically. On the other hand, transgenic mice expressing VP16 transgenes at postimplantation stages are viable. These results suggest a differential sensitivity to VP16 expression in different cell types and stages of development. The reduction of embryo survival by VP16 implicates herpes virus infection as a potential cause of infertility. Mol. Reprod. Dev. 55:37–46, 2000. © 2000 Wiley‐Liss, Inc.