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Gene Review

Tg  -  thyroglobulin

Mus musculus

Synonyms: Tgn, Thyroglobulin, cog
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Disease relevance of Tg


Psychiatry related information on Tg

  • The heavy (H) and light (L) chains of murine monoclonal autoantibody 62 reacting with thyroglobulin independently express idiotypic (Id) determinants that are very similar if not identical with the Id62 expressed on the intact protein [6].

High impact information on Tg

  • Also a large supply of iodine and of thyroid hormone is stored into the Tg molecule and available for secretion on demand [7].
  • Characteristically these patients exhibit hereditary congenital goiter with relatively low Tg levels that do not increase after stimulation with bovine TSH [7].
  • In another subject molecular studies revealed that exon 4 was missing from the major Tg transcript due to a cytosine to guanine transversion at position minus 3 in the acceptor splice site of intron 3 [7].
  • The point mutation is removed by the preferential accumulation of a 171 nt deleted Tg mRNA [7].
  • We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and beta-galactosidase [8].

Chemical compound and disease context of Tg


Biological context of Tg

  • We report in this paper the cloning of TTF-2, a DNA binding protein that recognizes sites on both Tg and TPO promoters [12].
  • These results indicate that the structural gene for thyroglobulin is on chromosome 15 and suggest that a mutation at the site of the TG gene is the basis of the cog defect [1].
  • Consistent with this hypothesis, the DN CREB transgene inhibited the expression of an array of genes including thyroglobulin, thyroperoxidase, and the TSH receptor in semiquantitative RT-PCR experiments [13].
  • Thyroid gland morphogenesis initiates normally, but follicle formation and thyroglobulin processing are abnormal at late gestation [14].
  • Comparison of the complete sequences reveals that cog/cog mice express a Leu-2263 --> Pro missense mutation in the acetylcholinesterase-homology domain of Tg [4].

Anatomical context of Tg

  • Expression of thyroglobulin (Tg) and thyroperoxidase (TPO) genes in thyroid follicular cells occurs in the mouse at embryonic day (E)14 [12].
  • Heterologous expression studies in COS cells indicate that cog Tg exhibits a severe defect in exit from the ER [4].
  • This study reaffirms the predictive value of A(k)-binding motifs in epitope mapping and doubles the number of known pathogenic T cell determinants in Tg that are now found scattered throughout the length of this large autoantigen [5].
  • In addition, four of 22 tumors co-express thyroglobulin (a non-neuroendocrine follicular epithelial cell marker) and calcitonin (a neuroendocrine marker) in a subset of the tumor cells [15].
  • The FRTL-5/TA cell line was the least differentiated one as thyroglobulin mRNA was detectable in only minute amounts and thyroid peroxidase expression could not be measured [16].

Associations of Tg with chemical compounds


Physical interactions of Tg


Regulatory relationships of Tg

  • 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 [21].
  • Effector cells from either IFN-gamma(+/+) or IFN-gamma(-/-) donor mice activated with mouse thyroglobulin and anti-IL-2R mAb induced severe granulomatous EAT [22].
  • To determine whether HMGI proteins are also required for in vivo thyroid carcinogenesis, mice carrying a disrupted HMGI-C gene (pygmy mice) were either treated with radioactive iodine or crossed with transgenic mice carrying the E7 papilloma virus oncogene under the transcriptional control of thyroglobulin gene promoter [23].

Other interactions of Tg


Analytical, diagnostic and therapeutic context of Tg

  • Site-directed mutagenesis of cog Tg to convert the single amino acid back to Leu-2263 restores normal Tg secretion [4].
  • Autoradiography showed 125I was incorporated only into Tg within recognizable follicular lumina of thyroids from +/cog mice [27].
  • Reverse transcriptase PCR showed that suppression of Pax-8 by Tg is correlated with reduced expression of bcl-2 apoptosis suppressor [26].
  • A panel of mouse-rat cell hybrids was used to determine the chromosomal localization of the rat thyroglobulin gene by the Southern blotting method [28].
  • Tissue studies confirm that there is an absent Tg peak at gel filtration, and virtually no immunoassayable Tg is present in the tissue extracts [7].


  1. The congenital goiter mutation is linked to the thyroglobulin gene in the mouse. Taylor, B.A., Rowe, L. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  2. Pax8 has a key role in thyroid cell differentiation. Pasca di Magliano, M., Di Lauro, R., Zannini, M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. Genetic deletion of sonic hedgehog causes hemiagenesis and ectopic development of the thyroid in mouse. Fagman, H., Grände, M., Gritli-Linde, A., Nilsson, M. Am. J. Pathol. (2004) [Pubmed]
  4. A single amino acid change in the acetylcholinesterase-like domain of thyroglobulin causes congenital goiter with hypothyroidism in the cog/cog mouse: a model of human endoplasmic reticulum storage diseases. Kim, P.S., Hossain, S.A., Park, Y.N., Lee, I., Yoo, S.E., Arvan, P. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Delineation of five thyroglobulin T cell epitopes with pathogenic potential in experimental autoimmune thyroiditis. Verginis, P., Stanford, M.M., Carayanniotis, G. J. Immunol. (2002) [Pubmed]
  6. Independent expression of a regulatory idiotype on heavy and light chains. A further immunochemical analysis with anti-heavy and anti-light chain antibodies. Zanetti, M., Rogers, J. J. Immunol. (1987) [Pubmed]
  7. Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism. Medeiros-Neto, G., Targovnik, H.M., Vassart, G. Endocr. Rev. (1993) [Pubmed]
  8. Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction. Witsch, E.J., Cao, H., Fukuyama, H., Weigert, M. J. Exp. Med. (2006) [Pubmed]
  9. A thyroxine-containing peptide can induce murine experimental autoimmune thyroiditis. Hutchings, P.R., Cooke, A., Dawe, K., Champion, B.R., Geysen, M., Valerio, R., Roitt, I.M. J. Exp. Med. (1992) [Pubmed]
  10. Effect of the synthetic immunomodulator, linomide, on experimental models of thyroiditis. Hutchings, P., Hedlund, G., Dawe, K., Howlett, S., Cooke, A. Immunology (1999) [Pubmed]
  11. Results of passive and active immunization directed against ferric aerobactin in experimental enterobacterial infections in mice and chickens. Le Roy, D., Crouzier, C., Dho-Moulin, M., Dumont, A.S., Bouchet, A., Lafont, J.P., Andremont, A. Res. Microbiol. (1995) [Pubmed]
  12. TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation. Zannini, M., Avantaggiato, V., Biffali, E., Arnone, M.I., Sato, K., Pischetola, M., Taylor, B.A., Phillips, S.J., Simeone, A., Di Lauro, R. EMBO J. (1997) [Pubmed]
  13. A dominant negative CREB (cAMP response element-binding protein) isoform inhibits thyrocyte growth, thyroid-specific gene expression, differentiation, and function. Nguyen, L.Q., Kopp, P., Martinson, F., Stanfield, K., Roth, S.I., Jameson, J.L. Mol. Endocrinol. (2000) [Pubmed]
  14. Perturbed thyroid morphology and transient hypothyroidism symptoms in Hoxa5 mutant mice. Meunier, D., Aubin, J., Jeannotte, L. Dev. Dyn. (2003) [Pubmed]
  15. Expression of v-Ha-ras driven by the calcitonin/calcitonin gene-related peptide promoter: a novel transgenic murine model for medullary thyroid carcinoma. Johnston, D., Hatzis, D., Sunday, M.E. Oncogene (1998) [Pubmed]
  16. Thyrotropin dependent and independent thyroid cell lines selected from FRTL-5 derived tumors grown in nude mice. Ossendorp, F.A., Bruning, P.F., Schuuring, E.M., Van Den Brink, J.A., van der Heide, D., De Vijlder, J.J., De Bruin, T.W. Endocrinology (1990) [Pubmed]
  17. Defining thyrotropin-dependent and -independent steps of thyroid hormone synthesis by using thyrotropin receptor-null mice. Marians, R.C., Ng, L., Blair, H.C., Unger, P., Graves, P.N., Davies, T.F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. Gene expression profile in thyroid of transgenic mice overexpressing the adenosine receptor 2a. Goffard, J.C., Jin, L., Mircescu, H., Van Hummelen, P., Ledent, C., Dumont, J.E., Corvilain, B. Mol. Endocrinol. (2004) [Pubmed]
  19. Inherited congenital goiter in mice. Beamer, W.G., Maltais, L.J., DeBaets, M.H., Eicher, E.M. Endocrinology (1987) [Pubmed]
  20. Syngeneic sensitization of mouse lymphocytes on monolayers of thyroid epithelial cells. VII. Generation of thyroid-specific cytotoxic effector cells. Salamero, J., Charreire, J. Cell. Immunol. (1985) [Pubmed]
  21. 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]
  22. IFN-gamma-deficient mice develop severe granulomatous experimental autoimmune thyroiditis with eosinophil infiltration in thyroids. Tang, H., Sharp, G.C., Peterson, K.P., Braley-Mullen, H. J. Immunol. (1998) [Pubmed]
  23. HMGI-C gene expression is not required for in vivo thyroid cell transformation. Scala, S., Portella, G., Vitagliano, D., Ledent, C., Chiappetta, G., Giancotti, V., Dumont, J., Fusco, A. Carcinogenesis (2001) [Pubmed]
  24. The NXSM recombinant inbred strains of mice: genetic profile for 58 loci including the Mtv proviral loci. Eicher, E.M., Lee, B.K. Genetics (1990) [Pubmed]
  25. Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells. Ledent, C., Denef, J.F., Cottecchia, S., Lefkowitz, R., Dumont, J., Vassart, G., Parmentier, M. Endocrinology (1997) [Pubmed]
  26. Thyroglobulin increases cell proliferation and suppresses Pax-8 in mesangial cells. Sellitti, D.F., Suzuki, K., Doi, S.Q., LaGranha, C., Machado, M., Matos, T., Kohn, L.D. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  27. Mutant gene-induced disorders of structure, function and thyroglobulin synthesis in congenital goitre (cog/cog) in mice. Adkison, L.R., Taylor, S., Beamer, W.G. J. Endocrinol. (1990) [Pubmed]
  28. The thyroglobulin gene resides on chromosome 8 in man and on chromosome 7 in the rat. Brocas, H., Szpirer, J., Lebo, R.V., Levan, G., Szpirer, C., Cheung, M.C., Vassart, G. Cytogenet. Cell Genet. (1985) [Pubmed]
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