ArticleMolecular and cellular biology1995
A truncated herpes simplex virus thymidine kinase phosphorylates thymidine and nucleoside analogs and does not cause sterility in transgenic mice.
Article in Molecular and cellular biology, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 61 citations in OpenAlex.
- Improved vector toolkit for genome writing in mammalian cells.bioRxiv : the preprint server for biology · 2026Article
- Unraveling Glioblastoma: TME Implication and Gene Therapy Advances.Current gene therapy · 2025Review
- Cancer-Associated Fibroblasts Suppress Cancer Development: The Other Side of the Coin.Frontiers in cell and developmental biology · 2021Review
- Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma.Neuro-oncology · 2019Article
- Increased Cytotoxicity of Herpes Simplex Virus Thymidine Kinase Expression in Human Induced Pluripotent Stem Cells.International journal of molecular sciences · 2019Article
- Ex Vivo Selection of Transduced Hematopoietic Stem Cells for Gene Therapy of β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- FSP1(+) fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells.Scientific reports · 2015Article
- A Dual-reporter system for real-time monitoring and high-throughput CRISPR/Cas9 library screening of the hepatitis C virus.Scientific reports · 2015Article
- Suicide gene approach using a dual-expression lentiviral vector to enhance the safety of ex vivo gene therapy for bone repair.Gene therapy · 2014Article
- Developing genetically engineered mouse models to study tumor suppression.Current protocols in mouse biology · 2012Article
- Cancer suicide gene therapy with TK.007: superior killing efficiency and bystander effect.Journal of molecular medicine (Berlin, Germany) · 2011Article
- FSP1+ fibroblasts promote skin carcinogenesis by maintaining MCP-1-mediated macrophage infiltration and chronic inflammation.The American journal of pathology · 2011Article
- Nonintegrating foamy virus vectors.Journal of virology · 2010Article
- Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
- Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2006Article
- Recovery of myelin after induction of oligodendrocyte cell death in postnatal brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
- A DNA recombination-based approach to eliminate papillomavirus infection.Gene therapy · 2005Article
- A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging.European journal of nuclear medicine and molecular imaging · 2004Article
- Turning immunological memory into amnesia by depletion of dividing T cells.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Adenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent CCNU.Cancer gene therapy · 2001Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dividing eukaryotic cells expressing the herpes simplex virus type 1 thymidine kinase (TK) gene are sensitive to the cytotoxic effect of nucleoside analogs such as acyclovir or ganciclovir (GCV). Transgenic mice with cell-targeted expression of this conditional toxin have been used to create animals with temporally controlled cell-specific ablation. In these animal models, which allow the study of the physiological importance of a cell type, males are sterile. In this study, we showed that this phenomenon is due to testis-specific high-level expression of short TK transcripts initiated mainly upstream of the second internal ATG of the TK gene. This expression is DNA methylation independent. To obtain a suicide gene that does not cause male infertility, we generated and analyzed the properties of a truncated TK (delta TK) lacking the sequences upstream of the second ATG. We showed that when expressed at sufficient levels, the functional properties of delta TK are similar to those of TK in terms of thymidine or GCV phosphorylation. This translated into a similar GCV-dependent toxicity for delta TK- or TK-expressing cells, both in vitro and in transgenic mice. However, delta TK behaved differently from TK in two ways. First, it did not cause sterility in delta TK transgenic males. Second, low-level delta TK RNA expression did not confer sensitivity to GCV. The uses of delta TK in cell-specific ablation in transgenic mice and in gene therapy are discussed.
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