Endocrine Abstracts

Background: The study aimed to establish a mouse model of Graves’ disease (GD) with Graves’ ophthalmopathy (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 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, 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 (HE) staining of relevant tissues were performed.

Results: A total of 60% of mice (3/5, one mouse died) in the pcDNA3.1/TSHR-289(+) group developed GD+GO. In the pcDNA3.1/TSHR-289(+) and pcDNA3.1/IGF-1Rα (+) groups, 83.3% of mice (5/6) developed GD+GO. Mice in the pcDNA3.1/IGF-1Rα (+) 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 blood glucose of the mice in each group had no significant difference. 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, retrobulbar muscles, heart, and liver of these mice showed varying inflammatory infiltration, interstitial muscle edema, and hepatic vein congestion. 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 pcDNA3.1/TSHR-289(+) 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.

Keywords: Graves’ disease, Graves’ ophthalmopathy, IGF-1R, TSHR