Mouse model of Graves' orbitopathy induced by the immunization with TSHR A and IGF-1R α subunit gene.

Autor: Wu R; Department of Nuclear Medicine, General Hospital of Tianjin Medical University, 154 Anshan Road, Heping, Tianjin, 300052, China.; Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Jing'an, Shanghai, 200072, China., Li N; Department of Nuclear Medicine, General Hospital of Tianjin Medical University, 154 Anshan Road, Heping, Tianjin, 300052, China., Wang X; Department of Nuclear Medicine, General Hospital of Tianjin Medical University, 154 Anshan Road, Heping, Tianjin, 300052, China., Wang S; Department of Nuclear Medicine, General Hospital of Tianjin Medical University, 154 Anshan Road, Heping, Tianjin, 300052, China., Tan J; Department of Nuclear Medicine, General Hospital of Tianjin Medical University, 154 Anshan Road, Heping, Tianjin, 300052, China., Wang R; Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Jing'an, Shanghai, 200072, China., Zheng W; Department of Nuclear Medicine, General Hospital of Tianjin Medical University, 154 Anshan Road, Heping, Tianjin, 300052, China. zhengw@tmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of endocrinological investigation [J Endocrinol Invest] 2024 Oct; Vol. 47 (10), pp. 2507-2519. Date of Electronic Publication: 2024 Apr 25.
DOI: 10.1007/s40618-024-02344-z
Abstrakt: Purpose: The study aimed to establish a mouse model of Graves' disease (GD) with Graves' orbitopathy (GO; GD + GO) that can represent the clinical disease characteristics.
Methods: A eukaryotic expression plasmid of insulin-like growth factor 1 receptor (IGF-1R) α subunit (pcDNA3.1/IGF-1Rα) and a thyrotropin receptor (TSHR) A subunit plasmid (pcDNA3.1/TSHR-289) were injected in female BALB/c mice followed by immediate electroporation to induce a GD + GO model. Grouping was performed according to the frequency of injection (2- to 4-week intervals) and type of injected plasmids: T: pcDNA3.1/TSHR-289( +), I: pcDNA3.1/IGF-1Rα( +), or co-injection T + I: pcDNA3.1/TSHR-289( +) and pcDNA3.1/IGF-1Rα( +). Serum TSH, T4, TSAb, TSBAb, body weight, and blood glucose levels were evaluated. Thyroid 99m TcO 4- imaging and retrobulbar magnetic resonance imaging (MRI) were performed, and bilateral eye muscle volumes were measured. Immunohistochemistry and hematoxylin-eosin staining were performed on the relevant tissues, and semi-quantitative analysis was performed.
Results: A total of 60% of mice (3/5, one mouse died) in the T group developed GD + GO. In the T + I group, 83.3% of mice (5/6) developed GD + GO. Mice in the I group did not develop GD. Compared with the control group, serum T4, TSAb, and TSBAb of the mice in the GD + GO model groups were increased to varying degrees (P < 0.05), and serum TSH and body weight were significantly lower compared to the control group (P < 0.05). The thyroid uptake capacity of 99m TcO 4- and the volume of eye muscle of mice in the GD + GO group were significantly higher compared to the control group (P < 0.05). The thyroid and retrobulbar muscles of these mice showed varying inflammatory infiltration and interstitial muscle edema. The severity of GD + GO in the co-injection group was not related to injection frequency; however, GD and ocular signs in co-injection mice were more severe compared to the T group.
Conclusions: We successfully induced a GD + GO mouse model by a repeated co-injection of pcDNA3.1/IGF-1Rα and pcDNA3.1/TSHR-289 plasmids. Injection of pcDNA3.1/IGF-1Rα alone failed to induce GD. Co-injection of two plasmids induced more severe GD + GO than pcDNA3.1/TSHR-289( +) alone.
(© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)
Databáze: MEDLINE
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