Cloning and characterization of murine thyroglobulin cDNA

Thyroglobulin is used to induce in mice experimental autoimmune thyroiditis (EAT), a model for Hashimoto thyroiditis. Because murine thyroglobulin is a more potent inducer of EAT than heterologous thyroglobulins, it has been hypothesized that it contains unique pathogenic epitopes. The validation of this hypothesis has been hampered by the lack of the murine thyroglobulin sequence. To identify murine-specific areas in thyroglobulin, we cloned, by reverse transcriptase PCR, and sequenced the complete murine thyroglobulin cDNA. This encodes a polypeptide of 2748 amino acids that is 73.5 and 71.8% identical to bovine and human thyroglobulin, respectively. Six regions are unique to each species. We also analyzed through EpiMer the sequences able to bind to the I-E(k) major histocompatibility allele and, therefore, function as T cell epitopes. EpiMer analysis showed seven murine-specific T cell epitopes in thyroglobulin. The availability of the complete murine thyroglobulin sequence should promote the understanding of the pathogenesis and immunoregulation of EAT.