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 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.
Heyman
R A
RA
Howard Hughes Medical Institute, San Diego, CA 92138.
Borrelli
E
E
Lesley
J
J
Anderson
D
D
Richman
D D
DD
Baird
S M
SM
Hyman
R
R
Evans
R M
RM
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
D000945:Antigens, Differentiation, T-Lymphocyte; D013937:Thymidine Kinase; D015774:Ganciclovir; D000212:Acyclovir