Thymidine Kinase Obliteration: Creation of Transgenic Mice with Controlled Immune Deficiency

The cell-specific expression of herpes simplex virus 1 thymidine kinase (HSV-1-tk) has provided a simple and highly efficient technique to achieve conditional ablation of targeted cell types in transgenic mice. The ablation is induced by treating transgenic animals expressing HSV-1-tk with the antih...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1989-04, Vol.86 (8), p.2698-2702
Main Authors: Heyman, Richard A., Borrelli, Emiliana, Lesley, Jayne, Anderson, Deborah, Richman, Douglas D., Baird, Stephen M., Hyman, Robert, Evans, Ronald M.
Format: Article
Language:English
Subjects:
Acyclovir - administration & dosage
Acyclovir - analogs & derivatives
Acyclovir - toxicity
Analytical, structural and metabolic biochemistry
Animals
Antigens, Differentiation, T-Lymphocyte - analysis
B lymphocytes
Biological and medical sciences
Cell lines
Cell Survival
Cells
Disease Models, Animal
Enhancer Elements, Genetic
Enzymes and enzyme inhibitors
Fundamental and applied biological sciences. Psychology
Ganciclovir
Immunologic Deficiency Syndromes - embryology
Immunologic Deficiency Syndromes - genetics
Lymphoid Tissue - physiology
Mice
Mice, Transgenic - immunology
Nucleosides
Simplexvirus - enzymology
Simplexvirus - genetics
Spleen
Stem cells
T lymphocytes
Thymidine Kinase - genetics
Thymocytes
Time Factors
Tissue Distribution
Transferases
Transgenic animals
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Summary:The cell-specific expression of herpes simplex virus 1 thymidine kinase (HSV-1-tk) has provided a simple and highly efficient technique to achieve conditional ablation of targeted cell types in transgenic mice. The ablation is induced by treating transgenic animals expressing HSV-1-tk with the antiherpetic drug ganciclovir. In lymphoid tissues of mice expressing HSV-1-tk from an immunoglobulin promoter, administration of ganciclovir leads to massive destruction of B-and T-cell lineages. Tissues not expressing HSV-1-tk are insensitive to drug treatment. After depletion of >99% of total thymocytes, a number of progenitor cells remain that are able to repopulate all T-cell lineages within 7 days. The ability to control and direct ablation allows for creation of conditional mutant phenotypes at precise periods of development. This technique also provides a potential means to enrich stem cell populations as well as permitting the creation of animal models for particular pathological conditions.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.86.8.2698