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) c an be killed upon ganciclovir treatment. Likewise, conditional cell knock-o ut can be: obtained in transgenic mice expressing a TK gene placed under th e control of tissue-specific regulatory sequences. Such animals provide pow erful experimental systems for assessing the functional role of specific ce ll populations through their time-controlled ablation. However, whatever th e regulatory sequences used, a leaky toxic overexpression of TK in testis r enders male TK-transgenic mice sterile and prevents the generation of homoz ygous 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 regulato ry 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 fertil e homozygous mice harboring a functional Delta TK transgene. Delta TK shoul d thus dramatically facilitate the development of transgenic mice expressin g a conditional suicide gene.