RRC ID |
6534
|
著者 |
Kaneda T, Honda A, Hakozaki A, Fuse T, Muto A, Yoshida T.
|
タイトル |
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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ジャーナル |
Endocrinology
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Abstract |
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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巻・号 |
148(5)
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ページ |
2335-44
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公開日 |
2007-5-1
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DOI |
10.1210/en.2006-1077
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PII |
en.2006-1077
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PMID |
17255207
|
MeSH |
Animals
Autoantibodies / blood
Autoantibodies / immunology
CHO Cells
Cell Line
Chronic Disease
Cricetinae
Cricetulus
Disease Models, Animal*
Electroporation / methods*
Enzyme-Linked Immunosorbent Assay
Epitopes / immunology
Female
Graves Disease / immunology*
Graves Disease / pathology
Graves Disease / physiopathology
Hyperthyroidism / immunology*
Hyperthyroidism / pathology
Hyperthyroidism / physiopathology
Immunization / methods
Male
Mice
Mice, Inbred BALB C*
Mice, Inbred ICR
Receptors, Thyrotropin / genetics
Receptors, Thyrotropin / immunology
Thyroid Gland / immunology
Thyroid Gland / pathology
Thyroxine / blood
|
IF |
3.934
|
引用数 |
40
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WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
リソース情報 |
ヒト・動物細胞 |
|