Leading science, pioneering therapies
CRM Publications

Herpesvirus thymidine kinase transgenes that do not cause male sterility are aberrantly transcribed and translated in the testis.

TitleHerpesvirus thymidine kinase transgenes that do not cause male sterility are aberrantly transcribed and translated in the testis.
Publication TypeJournal Article
Year of Publication1998
AuthorsEllison AR, Bishop JO
JournalBiochim Biophys Acta
Date Published1998 Oct 23
KeywordsAnimals, Base Sequence, Cattle, Gene Expression Regulation, Genes, Reporter, Infertility, Male, Male, Mice, Mice, Transgenic, Molecular Sequence Data, Protein Biosynthesis, Testis, Thymidine Kinase, Transcription, Genetic, Viral Proteins

Mice that carry the wild-type herpes simplex virus type 1 (HSV1) thymidine kinase (tk) gene coupled to the bovine thyroglobulin (bTG) promoter (bTG-tk1 mice) express viral TK at a high level in the thyroid gland, and at an equally high level, ectopically, in the testis, which renders the males sterile. When the bTG promoter was coupled either to a variant of HSV1-tk (differing from the wild type in 2 nucleotides) (bTG-tk1alpha mice) or to the herpes simplex virus type 2 (HSV2) tk gene (bTG-tk2 mice) viral TK was expressed at high levels in the thyroid gland, 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 exhibited a 1.3 kb RNA initiated at or near the bTG cap site. Testes of all mice exhibited mainly 5'-end-shortened RNAs (bTG-tk1 and bTG-tk1alpha mice, approx. 1.2 kb and 0.9 kb; bTG-tk2 mice, approx. 1.2 kb) initiated 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-tk1alpha mice contained the full-length HSV-TK protein and a truncated variant previously shown to originate at a non-ATG start codon. Testes of these mice exhibited both proteins but relatively less of the full-length protein. We attribute the high level of viral TK in the testes of bTG-tk1 mice to the expression of a predominant protein of Mr 39000 that originates from ATG-2. Thyroid and testis of bTG-tk2 mice contained only the full-length HSV2-TK protein.

Alternate JournalBiochim. Biophys. Acta
PubMed ID9767091