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25-04-2024 | Hyperthyroidism | Original Article

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

Authors: R. Wu, N. Li, X. Wang, S. Wang, J. Tan, R. Wang, W. Zheng

Published in: Journal of Endocrinological Investigation

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Abstract

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 99mTcO4− 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 99mTcO4− 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.
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Literature
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go back to reference Moshkelgosha S, So PW, Deasy N, Diaz-Cano S, Banga JP (2013) Cutting edge: retrobulbar inflammation, adipogenesis, and acute orbital congestion in a preclinical female mouse model of graves’ orbitopathy induced by thyrotropin receptor plasmid-in vivo electroporation. Endocrinology 154(9):3008–3015. https://doi.org/10.1210/en.2013-1576CrossRefPubMed Moshkelgosha S, So PW, Deasy N, Diaz-Cano S, Banga JP (2013) Cutting edge: retrobulbar inflammation, adipogenesis, and acute orbital congestion in a preclinical female mouse model of graves’ orbitopathy induced by thyrotropin receptor plasmid-in vivo electroporation. Endocrinology 154(9):3008–3015. https://​doi.​org/​10.​1210/​en.​2013-1576CrossRefPubMed
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go back to reference Wu R, Zheng W, Li N, Rui Z, Zhou Y, Wang X (2021) Construction of recombinant eukaryotic expression plasmid encoding IGF-1R α subunit gene. Shandong Med J 61(16):1–5 Wu R, Zheng W, Li N, Rui Z, Zhou Y, Wang X (2021) Construction of recombinant eukaryotic expression plasmid encoding IGF-1R α subunit gene. Shandong Med J 61(16):1–5
Metadata
Title
Mouse model of Graves’ orbitopathy induced by the immunization with TSHR A and IGF-1R α subunit gene
Authors
R. Wu
N. Li
X. Wang
S. Wang
J. Tan
R. Wang
W. Zheng
Publication date
25-04-2024
Publisher
Springer International Publishing
Keyword
Hyperthyroidism
Published in
Journal of Endocrinological Investigation
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-024-02344-z
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