| An improved Graves' disease model established by using in vivo electroporation exhibited long-term immunity to hyperthyroidism in BALB/c mice. | |
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MedLine Citation:
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PMID: 17255207 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In Graves' disease, the overstimulation of the thyroid gland and hyperthyroidism are caused by autoantibodies directed against the TSH receptor (TSHR) that mimics the action of TSH. The establishment of an animal model is an important step to study the pathophysiology of autoimmune hyperthyroidism and for immunological analysis. In this study, we adopted the technique of electroporation (EP) for genetic immunization to achieve considerable enhancement of in vivo human TSHR (hTSHR) expression and efficient induction of hyperthyroidism in mice. In a preliminary study using beta-galactosidase (beta-gal) expression vectors, beta-gal introduced into the muscle by EP showed over 40-fold higher enzymatic activity than that introduced via previous direct gene transfer methods. The sustained hTSHR mRNA expression derived from cDNA transferred by EP was detectable in muscle tissue for at least 2 wk by RT-PCR. Based on these results, we induced hyperthyroidism via two expression vectors inserted with hTSHR or hTSHR289His cDNA. Consequently, 12.0-31.8% BALB/c mice immunized with hTSHR and 79.2-95.7% immunized with hTSHR289His showed high total T(4) levels due to the TSHR-stimulating antibody after three to four times repeated immunization by EP, and thyroid follicles of which were hyperplastic and had highly irregular epithelium. Moreover, TSHR-stimulating antibody surprisingly persisted more than 8 months after the last immunization. These results demonstrate that genetic immunization by in vivo EP is more efficient than previous procedures, and that it is useful for delineating the pathophysiology of Graves' disease. |
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Authors:
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Toshio Kaneda; Asako Honda; Atsushi Hakozaki; Tetsuya Fuse; Akihiro Muto; Tadashi Yoshida |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-01-25 |
Journal Detail:
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Title: Endocrinology Volume: 148 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-04-20 Completed Date: 2007-06-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 2335-44 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathophysiology, Hoshi University, Shinagawa, Tokyo 142-8501, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoantibodies / blood, immunology CHO Cells Cell Line Chronic Disease Cricetinae Cricetulus Disease Models, Animal* Electroporation / methods* Enzyme-Linked Immunosorbent Assay Epitopes / immunology Female Graves Disease / immunology*, pathology, physiopathology Hyperthyroidism / immunology*, pathology, physiopathology Immunization / methods Male Mice Mice, Inbred BALB C* Mice, Inbred ICR Receptors, Thyrotropin / genetics, immunology Thyroid Gland / immunology, pathology Thyroxine / blood |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/Epitopes; 0/Receptors, Thyrotropin; 7488-70-2/Thyroxine |
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