Fertile homozygous transgenic mice expressing a functional truncated herpes simplex thymidine kinase delta TK gene.
Dividing cells expressing the Herpes simplex type 1 thymidine kinase (TK) can be killed upon ganciclovir treatment. Likewise, conditional cell knock-out can be obtained in transgenic mice expressing a TK gene placed under the control of tissue-specific regulatory sequences. Such animals provide powerful experimental systems for assessing the functional role of specific cell populations through their time-controlled ablation. However, whatever the regulatory sequences used, a leaky toxic overexpression of TK in testis renders male TK-transgenic mice sterile and prevents the generation of homozygous TK-expressing animals. To solve this problem, we designed a truncated TK variant (delta TK) not expressed in the testis. We generated transgenic mice expressing delta TK under the control of lymphocyte-specific regulatory sequences derived from the CD4 gene. The delta TK protein expressed in T-lymphocytes allowed the conditional ablation of activated T-cells in vitro and in vivo. Importantly, for one transgenic line we could generate fertile homozygous mice harboring a functional delta TK transgene. delta TK should thus dramatically facilitate the development of transgenic mice expressing a conditional suicide gene.
Cohen
J L
JL
CNRS ESA, Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Paris, France.
Boyer
O
O
Salomon
B
B
Onclerco
R
R
Depetris
D
D
Lejeune
L
L
Dubus-Bonnet
V
V
Bruel
S
S
Charlotte
F
F
Mattéï
M G
MG
Klatzmann
D
D
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015704:CD4 Antigens / Q000235:genetics; D005260:Female; D005298:Fertility; D015774:Ganciclovir / Q000494:pharmacology; D005809:Genes, Regulator; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics*; D006720:Homozygote; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000201:enzymology / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D013737:Testis / Q000033:anatomy & histology / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; D015704:CD4 Antigens; D013937:Thymidine Kinase; D015774:Ganciclovir