The thyroid stimulating hormone receptor (TSHR) gene encodes a G protein-coupled receptor that is primarily expressed on the surface of thyroid follicular cells. It plays a key role in regulating thyroid function by binding to thyroid stimulating hormone (TSH), thereby activating downstream signaling pathways including the cAMP and phospholipase C cascades. These pathways stimulate the synthesis and secretion of thyroid hormones, which are essential for metabolic homeostasis. Mutations or dysregulation of TSHR are associated with a variety of thyroid diseases, such as Graves' disease (autoimmune hyperthyroidism) and congenital hypothyroidism. Due to the central role that TSHR plays in thyroid physiology, it is a key target for basic research and therapeutic development.
Human TSHR Adenoviral Particles are recombinant adenoviral vectors designed to deliver the TSHR gene to mammalian cells for functional studies or therapeutic applications. These particles take advantage of the high transduction efficiency and broad tropism of adenoviruses to enable stable expression of TSHR in both dividing and non-dividing cells. The adenoviral backbone is often modified to ensure safety, such as deletion of essential viral genes (e.g., E1/E3) to prevent replication and reduce immunogenicity. The TSHR sequence is inserted under the control of a strong promoter (e.g., CMV) to ensure high levels of protein expression. These particles are ideal for studying TSHR-mediated signaling, receptor-ligand interactions, or autoimmune mechanisms in vitro and in vivo.
Graves' orbitopathy (GO) is an autoimmune orbital disease. Dysfunction of the gut microbiota plays a crucial role in autoimmune diseases such as Graves' disease (GD) and GO. Here, researchers aimed to study the changes in the gut microbiota in GD/GO using a mouse model. The murine model of GD/GO was established by the challenge of adenovirus expressing thyroid-stimulating hormone (TSH) receptor (TSHR) (Ad-TSHR). The GD/GO model was successfully established, showing widened eyelids, proptosis and conjunctival redness, severe inflammatory infiltration between the thyroid gland and the extraocular muscle space, hypertrophy of the extraocular muscles, elevated thyroxine (T4) and decreased TSH, and positive staining for CD34, CD40, collagen I, and α-SMA. A total of 222 operational taxonomic units (OUTs) overlapped between the Ad-NC and Ad-TSHR group mice. The microbial composition of the samples in both groups was dominated by Bacteroidia and Clostridia, and the Ad-NC group had a significantly lower content of Bacteroidia and higher content of Clostridia. The results of KEGG orthologous homology analysis showed that dehydrogenase, aspartate, bile acid, chalcone synthase, acetyltransferase, glutamyl cyclotransferase, glycogenin, and 1-phosphatidylinositol-4-phosphate 5-kinase were different between the two groups. The results of enzyme commission (EC) analysis showed that several dehydrogenases, oxidases, and sulfur oxygen/reductases were different between the two groups. These research results can lay a solid experimental foundation for developing personalized treatment regimens for GD patients according to the individual gut microbiota.
First, the mouse GD/GO model was established by Ad-TSHR challenge. The mice were randomly divided into groups (Ad-TSHR, Ad-NC, and blank groups). The mice in the Ad-TSHR group were inoculated with TSHR adenovirus (Figure 1A). The morphology of mice in each group was observed at week 15, and representative images (lateral and front appearances) were taken. It was observed that mice in the Ad-TSHR group exhibited broadened eyelid, exophthalmos, and conjunctive redness (Figure 1B). Orbital and thyroid histopathological examination showed that the inflammatory infiltration between the thyroid gland and the extraocular muscle space of the Ad-TSHR group mice was severe, the extraocular muscle space was widened, and the vascular hyperplasia was more obvious than that of the blank group and the Ad-NC group. In addition, the degree of extraocular muscle hypertrophy in the Ad-TSHR group was better than that in the blank group (Figure 1C).
Figure 1. The murine model of GD/GO was established by immunization with thyroid-stimulating hormone receptor expressing adenovirus (Ad-TSHR). (Li Y, et al., 2023)
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Creative Biogene consistently delivers high-quality viral vectors. Their Human TSHR adenoviral particles met all expectations, and the provided documentation was comprehensive.
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