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) 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.
Ellison
A R
AR
Centre for Genome Research, University of Edinburgh, King's Buildings, Edinburgh EH9 3JQ, UK. are@itsa.ucsf.edu
Bishop
J O
JO
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D013737:Testis / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics*
D014764:Viral Proteins; C099241:thymidine kinase, Canid herpesvirus 1; D013937:Thymidine Kinase