An improved mouse model of Graves disease by once immunization with Ad-TSHR289

Abstract

The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.

The effect of hyperthyroidism on cognitive function, neuroinflammation, and necroptosis in APP/PS1 mice

“…To determine whether GD is associated with cognitive function, Ad-TSHR289 was initially injected into the 3-month-old APP/PS1 mice to establish a GD model as previously described (Fig. 1 A) [ 32 , 33 ]. At 6th, 11st, 23rd, 34th week, blood was collected for measurement of total thyroxine (TT4), TSH, TSH receptor antibody (TRAb), and aspartate aminotransferase (AST) levels.…”

“…To best investigate the role of hyperthyroidism in affecting cognitive function and microglia polarization, as well as necroptosis, a long-term hyperthyroidism of GD mouse model were established through injecting recombinant adenovirus overexpressing thyrotropin receptor A subunit 289 (Ad-TSHR289) in AD model mice (APP/PS1) [ 32 – 34 ]. So far, there is no effective treatment strategy to eliminate the pathological changes in the brain and restore cognitive function in AD patients.…”

Effectiveness and potential mechanism of Jiawei-Xiaoyao-San for hyperthyroidism: a systematic review

“…In recent years, our team has further optimized the modeling method. The improved single injection method has shortened the modeling time, and the modeling rate can reach 100% within 4 weeks after injection ( 61 ).…”

Insight Into Mouse Models of Hyperthyroidism

“…Studies have proven that the proportion of hyperthyroidism induced by adenovirus carrying TSHR-289 was significantly higher than that of full-length wild-type adenovirus containing TSHR (23). Besides, Tang et al immunized BALB/c female mice with an adenovirus expressing TSHR-289 once, and the rate of hyperthyroidism reached 100% at 6 week (17). This model reduced the number of immunizations, thus reducing the modelling time.…”

“…Besides, Tang et al. immunized BALB/c female mice with an adenovirus expressing TSHR-289 once, and the rate of hyperthyroidism reached 100% at 6 week ( 17 ). This model reduced the number of immunizations, thus reducing the modelling time.…”