HERPESVIRUS THYMIDINE KINASE TRANSGENES THAT DO NOT CAUSE MALE-STERILITY ARE ABERRANTLY TRANSCRIBED AND TRANSLATED IN THE TESTIS

Mice that carry the wild-type herpes simplex virus type 1 (HSV1) thymi dine kinase (tk) gene coupled to the bovine thyroglobulin (bTG) promot er (bTG-tk1 mice) express viral TK at a high level in the thyroid glan d, and at an equally high level, ectopically, in the testis, which ren ders the males sterile. When the bTG promoter was coupled either to a variant of HSV1-tk (differing from the wild type in 2 nucleotides) (bT G-tk1 alpha mice) or to the herpes simplex virus type 2 (HSV2) tk gene (bTC-tk2 mice) viral TK was expressed at high levels in the thyroid g land, and much lower levels in the testis, which causes a reduction in male fecundity rather than sterility. Here, we compare the expression of the three transgenes in the two tissues. Thyroids of all mice exhi bited a 1.3 kb RNA initiated at or near the bTG cap site. Testes of al l mice exhibited mainly 5'-end-shortened RNAs (bTG-tk1 and bTC-tk1 alp ha mice, approx. 1.2 kb and 0.9 kb; bTG-tk2 mice, approx. 1.2 kb) init iated from cryptic initiation sites in the HSV1-tk and HSV2-tk coding regions. Also, less abundant RNAs initiated near the bTG cap site were expressed from all three transgenes. Thyroids of bTG-tk1 and bTG-tk1 alpha mice contained the full-length HSV-TK protein and a truncated va riant previously shown to originate at a non-ATG start codon. Testes o f these mice exhibited both proteins but relatively less of the full-l ength protein. We attribute the high level of viral TK in the testes o f bTG-tk1 mice to the expression of a predominant protein of M-r 39 00 0 that originates from ATG-2. Thyroid and testis of bTG-tk2 mice conta ined only the full-length HSV2-TK protein. (C) 1998 Elsevier Science B .V. All rights reserved.