title: Thymidine kinase obliteration: creation of transgenic mice with controlled immune deficiency.
abstract: 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 greater than 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.
authors.affiliation: Howard Hughes Medical Institute, San Diego, CA 92138.
authors.forename: R A
authors.initials: RA
authors.lastname: Heyman
authors.forename: E
authors.initials: E
authors.lastname: Borrelli
authors.forename: J
authors.initials: J
authors.lastname: Lesley
authors.forename: D
authors.initials: D
authors.lastname: Anderson
authors.forename: D D
authors.initials: DD
authors.lastname: Richman
authors.forename: S M
authors.initials: SM
authors.lastname: Baird
authors.forename: R
authors.initials: R
authors.lastname: Hyman
authors.forename: R M
authors.initials: RM
authors.lastname: Evans
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002470:Cell Survival; D004195:Disease Models, Animal; D004742:Enhancer Elements, Genetic; D015774:Ganciclovir; D007153:Immunologic Deficiency Syndromes / Q000196:embryology / Q000235:genetics*; D008221:Lymphoid Tissue / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D013937:Thymidine Kinase; D015774:Ganciclovir; D000212:Acyclovir