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Gene Review

Tk1  -  thymidine kinase 1

Mus musculus

Synonyms: D530002A18Rik, Thymidine kinase, cytosolic, Tk-1, Tk1a, Tk1b
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Disease relevance of Tk1


Psychiatry related information on Tk1


High impact information on Tk1


Chemical compound and disease context of Tk1


Biological context of Tk1

  • DNA isolated from independent TK1-/- mutants was analyzed for loss of heterozygosity (LOH) at the Tk1 locus and two microsatellites, D11Mit48 and D11Nds7 [17].
  • From all of these analyses we can conclude that the small colony mutant phenotype is not caused by deletion of both Trp53 and Tk1 [18].
  • Inheritance in recombinant inbred (RI) strains of restriction fragment length variants (RFLVs) detected by probes specific for Gaa and Tk-1 showed tight linkage of both to Es-3 on mouse Chromosome (Chr) 11 [19].
  • Cells irradiated in the G1 and G2/M phases were most sensitive to the cytotoxic effects of radiation, while cells irradiated in the G2/M phase showed the highest mutant frequency at the thymidine kinase (Tk1) locus [17].
  • To determine whether small colonies might, however, include the deletion of both Trp53 and Tk we evaluated, using microsatellite marker analysis, a series of small colony mutants [18].

Anatomical context of Tk1

  • Afmid/Tk -deficient mice are known to develop sclerosis of glomeruli and to have an abnormal immune system [20].
  • Frequency of Tk and Hprt lymphocyte mutants and bone marrow micronuclei in B6C3F(1)/Tk+/- mice treated neonatally with zidovudine and lamivudine [21].
  • These results indicate that the selection of BrdUrd-resistant lymphocytes from Tk+/- mice may be used for assessing in vivo mutation in an endogenous, autosomal gene [22].
  • In order to determine the biological significance of the Tk gene, we created Tk(-/-) knockout (KO) mice through homologous recombination in mouse embryonic stem cells [5].
  • The alpha-subunit of the skeletal muscle sodium channel is encoded proximal to Tk-1 on mouse chromosome 11 [23].

Associations of Tk1 with chemical compounds


Physical interactions of Tk1


Regulatory relationships of Tk1

  • The high proportion of small colony tk -/- mutants induced by procarbazine together with the far weaker mutagenic response at the hemizygous hgprt locus in these same cells is interpreted in terms of a chromosomal or multi-gene mutational mechanism [16].
  • IL-3 regulates thymidine kinase activity, suggesting that alterations in dNTP metabolism after IL-3 deprivation could be a relevant event in the commitment of hemopoietic cells to apoptosis [30].
  • Strategies that have been employed successfully in animal models include adenoviral mediated expression of thymidine kinase under control of a thyroglobulin promoter, similarly expression of the cytokine IL-2, and perhaps most effectively, expression of IL-12 [31].
  • In contrast, the thymidine kinase (TK-1) promoter is also regulated by E2F3 but independent of TFE3 [32].
  • The genes encoding thymidine kinase (Tk-1) and p34cdc2 (cdc2) are regulated with kinetics similar to those observed for changes in the macromolecular state of E2F [33].

Other interactions of Tk1

  • The frequency of mutants with LOH at both Tk1 and D11Nds7 with no loss of GLK activity was high in all cell populations: There was no significant difference in the observed frequency of these mutants between the populations [17].
  • Loss of P53 heterozygosity is not responsible for the small colony thymidine kinase mutant phenotype in L5178Y mouse lymphoma cells [18].
  • Both Scn4a and Tk-1 showed clear linkage to mouse Chr 11 loci previously typed in this backcross, yielding the map order: TrJ-(Re, Hox-2, Krt-1)-Scn4a-Tk-1 [23].
  • On the other hand, removal of IL-3 from cultures of BAF3 cells resulted in down-regulation of thymidine kinase activity, rapid imbalance in dNTP levels, and apoptosis [12].
  • The mouse-lymphoma mutagenesis assay detects forward mutations at the heterozygous thymidine kinase (tk-1) locus in L5178Y tk+/- 3.7.2C cells [34].

Analytical, diagnostic and therapeutic context of Tk1


  1. Large mutagenic lesions are induced by photodynamic therapy in murine L5178Y lymphoblasts. Deahl, J.T., Oleinick, N.L., Evans, H.H. Photochem. Photobiol. (1993) [Pubmed]
  2. DNA-mediated cotransfer of unlinked mammalian cell markers into mouse L cells. Warrick, H., Hsiung, N., Shows, T.B., Kucherlapati, R. J. Cell Biol. (1980) [Pubmed]
  3. Activity of thymidylate synthetase, thymidine kinase and galactokinase in primary and xenografted human colorectal cancers in relation to their chromosomal patterns. Bardot, V., Luccioni, C., Lefrançois, D., Muleris, M., Dutrillaux, B. Int. J. Cancer (1991) [Pubmed]
  4. Cotransfer and phenotypic stabilisation of syntenic and asyntenic mink genes into mouse cells by chromosome-mediated gene transfer. Sukoyan, M.A., Matveeva, N.M., Belyaev, N.D., Pack, S.D., Gradov, A.A., Shilov, A.G., Zhdanova, N.S., Serov, O.L. Mol. Gen. Genet. (1984) [Pubmed]
  5. Mice deficient for cytosolic thymidine kinase gene develop fatal kidney disease. Dobrovolsky, V.N., Bucci, T., Heflich, R.H., Desjardins, J., Richardson, F.C. Mol. Genet. Metab. (2003) [Pubmed]
  6. Analysis of large and small colony L5178Y tk-/- mouse lymphoma mutants by loss of heterozygosity (LOH) and by whole chromosome 11 painting: detection of recombination. Liechty, M.C., Scalzi, J.M., Sims, K.R., Crosby, H., Spencer, D.L., Davis, L.M., Caspary, W.J., Hozier, J.C. Mutagenesis (1998) [Pubmed]
  7. Transmission distortion and mosaicism in an unusual transgenic mouse pedigree. Palmiter, R.D., Wilkie, T.M., Chen, H.Y., Brinster, R.L. Cell (1984) [Pubmed]
  8. Gene transfer, expression, and molecular cloning of the human transferrin receptor gene. Kühn, L.C., McClelland, A., Ruddle, F.H. Cell (1984) [Pubmed]
  9. Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. Luciw, P.A., Bishop, J.M., Varmus, H.E., Capecchi, M.R. Cell (1983) [Pubmed]
  10. The adenovirus type 5 E1A transcriptional control region contains a duplicated enhancer element. Hearing, P., Shenk, T. Cell (1983) [Pubmed]
  11. Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Palmiter, R.D., Chen, H.Y., Brinster, R.L. Cell (1982) [Pubmed]
  12. Overexpression of a heterologous thymidine kinase delays apoptosis induced by factor deprivation and inhibitors of deoxynucleotide metabolism. Oliver, F.J., Collins, M.K., López-Rivas, A. J. Biol. Chem. (1997) [Pubmed]
  13. Bovine herpesvirus tegument protein VP22 enhances thymidine kinase/ganciclovir suicide gene therapy for neuroblastomas compared to herpes simplex virus VP22. Qiu, Z., Harms, J.S., Zhu, J., Splitter, G.A. J. Virol. (2004) [Pubmed]
  14. Bromate induces loss of heterozygosity in the thymidine kinase gene of L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cells. Harrington-Brock, K., Collard, D.D., Chen, T. Mutat. Res. (2003) [Pubmed]
  15. 5-Formyluracil and its nucleoside derivatives confer toxicity and mutagenicity to mammalian cells by interfering with normal RNA and DNA metabolism. Klungland, A., Paulsen, R., Rolseth, V., Yamada, Y., Ueno, Y., Wiik, P., Matsuda, A., Seeberg, E., Bjelland, S. Toxicol. Lett. (2001) [Pubmed]
  16. Procarbazine is a potent mutagen at the heterozygous thymidine kinase (tk +/-) locus of mouse lymphoma assay. Clive, D., Turner, N., Krehl, R. Mutagenesis (1988) [Pubmed]
  17. Induction of multilocus mutations at the Tk1 locus after X irradiation of L5178Y cells at different times in the mitotic cycle. Evans, H.H., Mencl, J., Ricanati, M., Horng, M.F., Chaudhry, M.A., Jiang, Q., Hozier, J., Liechty, M. Radiat. Res. (1996) [Pubmed]
  18. Loss of P53 heterozygosity is not responsible for the small colony thymidine kinase mutant phenotype in L5178Y mouse lymphoma cells. Clark, L.S., Harrington-Brock, K., Wang, J., Sargent, L., Lowry, D., Reynolds, S.H., Moore, M.M. Mutagenesis (2004) [Pubmed]
  19. Linkage of acid alpha-glucosidase (Gaa) and thymidine kinase (Tk-1) to esterase-3 (Es-3) on mouse chromosome 11. Martiniuk, F., Hirschhorn, R., D'Eustachio, P. Mamm. Genome (1991) [Pubmed]
  20. Effect of arylformamidase (kynurenine formamidase) gene inactivation in mice on enzymatic activity, kynurenine pathway metabolites and phenotype. Dobrovolsky, V.N., Bowyer, J.F., Pabarcus, M.K., Heflich, R.H., Williams, L.D., Doerge, D.R., Arvidsson, B., Bergquist, J., Casida, J.E. Biochim. Biophys. Acta (2005) [Pubmed]
  21. Frequency of Tk and Hprt lymphocyte mutants and bone marrow micronuclei in B6C3F(1)/Tk+/- mice treated neonatally with zidovudine and lamivudine. Von Tungeln, L.S., Hamilton, L.P., Dobrovolsky, V.N., Bishop, M.E., Shaddock, J.G., Heflich, R.H., Beland, F.A. Carcinogenesis (2002) [Pubmed]
  22. Tk+/- mouse model for detecting in vivo mutation in an endogenous, autosomal gene. Dobrovolsky, V.N., Casciano, D.A., Heflich, R.H. Mutat. Res. (1999) [Pubmed]
  23. The alpha-subunit of the skeletal muscle sodium channel is encoded proximal to Tk-1 on mouse chromosome 11. Ambrose, C., Cheng, S., Fontaine, B., Nadeau, J.H., MacDonald, M., Gusella, J.F. Mamm. Genome (1992) [Pubmed]
  24. Differential mutant quantitation at the mouse lymphoma tk and CHO hgprt loci. Moore, M.M., Harrington-Brock, K., Doerr, C.L., Dearfield, K.L. Mutagenesis (1989) [Pubmed]
  25. Regulation of the salvage pathway of deoxynucleotides synthesis in apoptosis induced by growth factor deprivation. Oliver, F.J., Collins, M.K., López-Rivas, A. Biochem. J. (1996) [Pubmed]
  26. Cyclin D1/cdk2 kinase is present in a G1 phase-specific protein complex Yi1 that binds to the mouse thymidine kinase gene promoter. Dou, Q.P., Molnar, G., Pardee, A.B. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  27. Structural and functional analysis of the promoter of the murine V gamma 1.1 T cell receptor gene. Ofir, R., Novick, I., Krup, M., Cleveland, J.L., Ihle, J.N., Weinstein, Y. Eur. J. Immunol. (1995) [Pubmed]
  28. A binding site for transcription factor E2F is a target for trans activation of murine thymidine kinase by polyomavirus large T antigen and plays an important role in growth regulation of the gene. Ogris, E., Rotheneder, H., Mudrak, I., Pichler, A., Wintersberger, E. J. Virol. (1993) [Pubmed]
  29. Induction of interleukin-12 p40 transcript by CD40 ligation via activation of nuclear factor-kappaB. Yoshimoto, T., Nagase, H., Ishida, T., Inoue, J., Nariuchi, H. Eur. J. Immunol. (1997) [Pubmed]
  30. dNTP pools imbalance as a signal to initiate apoptosis. Oliver, F.J., Collins, M.K., López-Rivas, A. Experientia (1996) [Pubmed]
  31. Viral mediated gene therapy for the management of metastatic thyroid carcinoma. DeGroot, L.J., Zhang, R. Curr. Drug Targets Immune Endocr. Metabol. Disord. (2004) [Pubmed]
  32. Combinatorial gene control involving E2F and E Box family members. Giangrande, P.H., Zhu, W., Rempel, R.E., Laakso, N., Nevins, J.R. EMBO J. (2004) [Pubmed]
  33. The macromolecular state of the transcription factor E2F and glucocorticoid regulation of c-myc transcription. Rhee, K., Ma, T., Thompson, E.A. J. Biol. Chem. (1994) [Pubmed]
  34. Sequence analysis of tka(-)-1 and tkb(+)-1 alleles in L5178Y tk+/- mouse-lymphoma cells and spontaneous tk-/- mutants. Liechty, M.C., Rauchfuss, H.S., Lugo, M.H., Hozier, J.C. Mutat. Res. (1993) [Pubmed]
  35. Molecular cloning and structural analysis of murine thymidine kinase genomic and cDNA sequences. Lin, P.F., Lieberman, H.B., Yeh, D.B., Xu, T., Zhao, S.Y., Ruddle, F.H. Mol. Cell. Biol. (1985) [Pubmed]
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