title: Fertile homozygous transgenic mice expressing a functional truncated herpes simplex thymidine kinase delta TK gene.
abstract: 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.
authors.affiliation: CNRS ESA, Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Paris, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Cohen
authors.forename: O
authors.initials: O
authors.lastname: Boyer
authors.forename: B
authors.initials: B
authors.lastname: Salomon
authors.forename: R
authors.initials: R
authors.lastname: Onclerco
authors.forename: D
authors.initials: D
authors.lastname: Depetris
authors.forename: L
authors.initials: L
authors.lastname: Lejeune
authors.forename: V
authors.initials: V
authors.lastname: Dubus-Bonnet
authors.forename: S
authors.initials: S
authors.lastname: Bruel
authors.forename: F
authors.initials: F
authors.lastname: Charlotte
authors.forename: M G
authors.initials: MG
authors.lastname: Mattéï
authors.forename: D
authors.initials: D
authors.lastname: Klatzmann
mesh_terms: 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*
chemical_list: D000998:Antiviral Agents; D015704:CD4 Antigens; D013937:Thymidine Kinase; D015774:Ganciclovir