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Gene Review

Tag  -  temporal alpha-galactosidase

Mus musculus

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Disease relevance of Tag


High impact information on Tag

  • The CaBP9K regulatory sequences directing the expression of the Tag gene possess an estradiol responsive element, and accordingly, development of the tumors was strictly under the control of estrogen [6].
  • The distinct cerebellar phenotypes of the SV4-6 lines correlate with specific Tag-induced Purkinje cell ablation as opposed to tumorigenesis [7].
  • However, after the transgene is expressed, RIP1-Tag4 mice are unable to mount a tumor-inhibiting response upon immunization, although Tag-specific cytotoxic T cells can still be demonstrated in vitro [5].
  • Indeed, RIP1-Tag4 mice immunized with Tag by SV40 infection prior to the time of endogenous transgene expression also mount an effective in vivo cellular immune response to the Tag-expressing pancreatic beta cells, and Tag-induced tumor growth is significantly delayed (up to 1 year) [5].
  • Transgenic mice expressing T antigen (Tag) in pancreatic beta cells establish systemic tolerance toward this self-protein [8].

Chemical compound and disease context of Tag

  • Forty-eight transgenic BLH-SV40 Tag retinoblastoma mice were administered five intravitreal injections of carboplatin in one eye [9].
  • Although testosterone treatment was able to induce interstitial cell hyperplasia in gonads of the Inh-alpha/Tag mice, direct gonadotropin action is responsible for gonadal and adrenal tumorigenesis [10].
  • The single (Inhalpha/Tag) and double TG (Inhalpha/TK-Inhalpha/Tag) mice, both bearing gonadal tumors, were treated at the age of 5.5-6.5 months with ganciclovir (GCV, 150 mg/kg body weight twice daily i.p.) for 14 days, or with aciclovir (ACV, 300-400 mg/kg body weight per day perorally) for 2 months [11].

Biological context of Tag

  • These mice have impaired antibody responses to Tag, show diminished Tag-specific T-cell proliferation, and evidence an inability to generate Tag-specific cytotoxic T cells [8].
  • The self-tolerance in two families of rat insulin promoter (RIP)-Tag mice, expressing different levels of Tag protein, has been characterized [8].
  • Twenty-one of 32 (66%) mice aged > or = 6 months and 15 of 17 (88%) mice aged > or = 9 months developed metastatic tumors, as confirmed by histology and/or Tag immunohistochemistry [12].
  • Thus, the expression of Tag in intestinal goblet cells releases them from normal antiproliferative controls, causing their inappropriate entry into S phase even after they transverse the crypt/villus junction [13].
  • KIM-2 cells were generated using a temperature sensitive T-antigen (Tag) and studies at the permissive temperature (33 degrees C) have shown that a Tag binding protein was essential for this apoptotic response [14].

Anatomical context of Tag

  • To test this hypothesis we introduced an enhancerless Tag gene downstream of a LCR cassette into the germ lines of mice [3].
  • A line of mice was established (MUCTag6) that expressed Tag in intestinal goblet cells as determined by RNA blot and immunohistochemical analysis [13].
  • Whereas Tag is expressed uniformly in prostate epithelium, only an increasing subset of cells in prostatic intraepithelial neoplasia showed NE differentiation by chromogranin immunostaining [12].
  • Tyrp1-Tag mice that develop early vascularized tumors of the retinal pigment epithelium were crossed with tyrp1-FGFR1-DN mice that express dominant-negative FGF receptors in the retinal pigment epithelium to generate bigenic mice [15].
  • By contrast, at a later stage when tyrp1-Tag tumors rapidly expanded to fill the entire eye posterior chamber and migrate along the optic nerve toward the chiasma, bigenic tumors remained small and were poorly vascularized [15].

Associations of Tag with chemical compounds

  • As the expression of Tag transcripts is controlled by D-glucose, the structural and physiological characteristics of these cell lines can be studied in either quiescent or active growth conditions [16].
  • To study further the role of luteinizing hormone (LH) in gonadal and adrenal tumorigenesis, a double TG mouse model was generated by crossing the Inhalpha/Tag mice with mice producing constitutively elevated levels of LH (bLHbeta-CTP mice) [17].
  • To achieve efficient and regulated mutagenesis, we constructed Enhanced Retroviral Mutagen (ERM) vectors that contained several engineered sequences (e.g., an ERM Tag and a splice donor) controlled by a tetracycline-responsive promoter [18].
  • Replacement of D-glucose by neoglucogenic substrates (lactate, oxaloacetate) blunted the expression of Tag transcripts and induced arrest of cell growth [16].
  • Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice [19].

Physical interactions of Tag

  • Tag-p53 and Tag-pRb complexes were screened in 18 and 15 Tag positive tumor tissues, respectively [20].

Regulatory relationships of Tag


Other interactions of Tag

  • The d11137 Tag mutant protein, which inhibits pRb function without affecting p53, induced hepatic tumours [22].
  • In contrast, only one of the eight Tag/Ghr(-/-) mice exhibited atypia (P < 0.01, Fischer's exact test) [23].
  • In contrast, only a few differentiated cells were observed in the presence of TGF beta 1 and Tag [24].
  • Transgenic (TG) mice expressing the Simian virus 40 T-antigen under the control of the murine inhibin-alpha promoter (Inhalpha/Tag) develop granulosa and Leydig cell tumors at the age of 5-6 months, with 100% penetrance [17].
  • We conclude that in the Inhalpha/Tag tumor mouse model, elevated LH levels act as a tumor promoter, advancing gonadal and adrenal tumorigenesis [17].

Analytical, diagnostic and therapeutic context of Tag

  • In addition, the adoptive transfer of spleen cells from Tag-immune C57BL/6 mice resulted in a dramatic increase in the control of tumor progression in SV11 mice and was associated with the accumulation of CD8(+) T cells specific for multiple Tag epitopes in the brain [25].
  • In a classical vaccination protocol, Tag was administered with CpG-ODN as adjuvant [26].
  • The DNA synthesis, as well as the levels of inhibin-alpha and Tag mRNA expression, were significantly reduced by recombinant human inhibin A in cell cultures derived from the adrenal tumors [27].
  • Results from Northern blot analysis indicate that the expression of the T antigen gene (Tag) is dependent on the concentration of D-glucose in the medium and show that the L-PK construct has maintained its capacity for up- or down-regulation by carbohydrates [16].
  • In this study we investigated SV40 large T antigen (SV40 Tag) protein expression in mesothelioma cell lines, established in our laboratory, by Western blotting, immunoprecipitation, and immunocytochemistry using Tag-specific mouse monoclonal antibodies (mAbs) Ab-1 (or Pab 419) [28].


  1. Clonal deletion of simian virus 40 large T antigen-specific T cells in the transgenic adenocarcinoma of mouse prostate mice: an important role for clonal deletion in shaping the repertoire of T cells specific for antigens overexpressed in solid tumors. Zheng, X., Gao, J.X., Zhang, H., Geiger, T.L., Liu, Y., Zheng, P. J. Immunol. (2002) [Pubmed]
  2. Modulation of L-selectin ligand expression during an immune response accompanying tumorigenesis in transgenic mice. Onrust, S.V., Hartl, P.M., Rosen, S.D., Hanahan, D. J. Clin. Invest. (1996) [Pubmed]
  3. Rhabdomyosarcoma arising in transgenic mice harboring the beta-globin locus control region fused with simian virus 40 large T antigen gene. Teitz, T., Chang, J.C., Kitamura, M., Yen, T.S., Kan, Y.W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  4. L-selectin can facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis. Qian, F., Hanahan, D., Weissman, I.L. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Timely immunization subverts the development of peripheral nonresponsiveness and suppresses tumor development in simian virus 40 tumor antigen-transgenic mice. Ye, X., McCarrick, J., Jewett, L., Knowles, B.B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Estradiol-dependent uterine leiomyomas in transgenic mice. Romagnolo, B., Molina, T., Leroy, G., Blin, C., Porteux, A., Thomasset, M., Vandewalle, A., Kahn, A., Perret, C. J. Clin. Invest. (1996) [Pubmed]
  7. Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Feddersen, R.M., Ehlenfeldt, R., Yunis, W.S., Clark, H.B., Orr, H.T. Neuron (1992) [Pubmed]
  8. T-cell tolerance toward a transgenic beta-cell antigen and transcription of endogenous pancreatic genes in thymus. Jolicoeur, C., Hanahan, D., Smith, K.M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  9. Local carboplatin therapy in transgenic murine retinoblastoma. Harbour, J.W., Murray, T.G., Hamasaki, D., Cicciarelli, N., Hernández, E., Smith, B., Windle, J., O'Brien, J.M. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
  10. Long-term testosterone treatment prevents gonadal and adrenal tumorigenesis of mice transgenic for the mouse inhibin-alpha subunit promoter/simian virus 40 T-antigen fusion gene. Rilianawati, n.u.l.l., Kero, J., Paukku, T., Huhtaniemi, I. J. Endocrinol. (2000) [Pubmed]
  11. Gonadal tumors of mice double transgenic for inhibin-alpha promoter-driven simian virus 40 T-antigen and herpes simplex virus thymidine kinase are sensitive to ganciclovir treatment. Mikola, M.K., Rahman, N.A., Paukku, T.H., Ahtiainen, P.M., Vaskivuo, T.E., Tapanainen, J.S., Poutanen, M., Huhtaniemi, I.T. J. Endocrinol. (2001) [Pubmed]
  12. A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. Masumori, N., Thomas, T.Z., Chaurand, P., Case, T., Paul, M., Kasper, S., Caprioli, R.M., Tsukamoto, T., Shappell, S.B., Matusik, R.J. Cancer Res. (2001) [Pubmed]
  13. Mouse intestinal goblet cells expressing SV40 T antigen directed by the MUC2 mucin gene promoter undergo apoptosis upon migration to the villi. Gum, J.R., Hicks, J.W., Gillespie, A.M., Rius, J.L., Treseler, P.A., Kogan, S.C., Carlson, E.J., Epstein, C.J., Kim, Y.S. Cancer Res. (2001) [Pubmed]
  14. p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells. MacLaren, A.P., Chapman, R.S., Wyllie, A.H., Watson, C.J. Cell Death Differ. (2001) [Pubmed]
  15. The tyrp1-Tag/tyrp1-FGFR1-DN bigenic mouse: a model for selective inhibition of tumor development, angiogenesis, and invasion into the neural tissue by blockade of fibroblast growth factor receptor activity. Rousseau, B., Larrieu-Lahargue, F., Javerzat, S., Guilhem-Ducléon, F., Beermann, F., Bikfalvi, A. Cancer Res. (2004) [Pubmed]
  16. Functional properties of proximal tubule cell lines derived from transgenic mice harboring L-pyruvate kinase-SV40 (T) antigen hybrid gene. Lacave, R., Bens, M., Cartier, N., Vallet, V., Robine, S., Pringault, E., Kahn, A., Vandewalle, A. J. Cell. Sci. (1993) [Pubmed]
  17. High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-alpha-subunit promoter/Simian virus 40 T-antigen fusion gene. Mikola, M., Kero, J., Nilson, J.H., Keri, R.A., Poutanen, M., Huhtaniemi, I. Oncogene (2003) [Pubmed]
  18. Genetic screens in mammalian cells by enhanced retroviral mutagens. Liu, D., Yang, X., Yang, D., Songyang, Z. Oncogene (2000) [Pubmed]
  19. Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice. Liu, M.L., Shibata, M.A., Von Lintig, F.C., Wang, W., Cassenaer, S., Boss, G.R., Green, J.E. Oncogene (2001) [Pubmed]
  20. Simian virus 40 large tumor antigen forms specific complexes with p53 and pRb in human brain tumors. Zhen, H., Zhang, X., Zhang, Z., Fei, Z., He, X., Liang, J., Huang, W., Liu, X., Zhang, P. Chin. Med. J. (2001) [Pubmed]
  21. Hormonal regulation of proliferation of granulosa and Leydig cell lines derived from gonadal tumors of transgenic mice expressing the inhibin-alpha subunit promoter/simian virus 40 T-antigen fusion gene. Rilianawati, n.u.l.l., Rahman, N.A., Huhtaniemi, I. Mol. Cell. Endocrinol. (1999) [Pubmed]
  22. The amino-terminal region of SV40 large T antigen is sufficient to induce hepatic tumours in mice. Bennoun, M., Grimber, G., Couton, D., Seye, A., Molina, T., Briand, P., Joulin, V. Oncogene (1998) [Pubmed]
  23. Disruption of growth hormone signaling retards early stages of prostate carcinogenesis in the C3(1)/T antigen mouse. Wang, Z., Prins, G.S., Coschigano, K.T., Kopchick, J.J., Green, J.E., Ray, V.H., Hedayat, S., Christov, K.T., Unterman, T.G., Swanson, S.M. Endocrinology (2005) [Pubmed]
  24. Understanding mammary gland development through the imbalanced expression of growth regulators. Robinson, G.W., Smith, G.H., Gallahan, D., Zimmer, A., Furth, P.A., Hennighausen, L. Dev. Dyn. (1996) [Pubmed]
  25. Control of advanced choroid plexus tumors in SV40 T antigen transgenic mice following priming of donor CD8(+) T lymphocytes by the endogenous tumor antigen. Schell, T.D., Tevethia, S.S. J. Immunol. (2001) [Pubmed]
  26. CpG motifs as proinflammatory factors render autochthonous tumors permissive for infiltration and destruction. Garbi, N., Arnold, B., Gordon, S., Hämmerling, G.J., Ganss, R. J. Immunol. (2004) [Pubmed]
  27. Gonadectomy permits adrenocortical tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene: evidence for negative autoregulation of the inhibin alpha-subunit gene. Kananen, K., Markkula, M., Mikola, M., Rainio, E.M., McNeilly, A., Huhtaniemi, I. Mol. Endocrinol. (1996) [Pubmed]
  28. Absence of SV40 large T-antigen expression in human mesothelioma cell lines. Pilatte, Y., Vivo, C., Renier, A., Kheuang, L., Greffard, A., Jaurand, M.C. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
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