RRC ID 2060
Author Nagayama Y, Kita-Furuyama M, Ando T, Nakao K, Mizuguchi H, Hayakawa T, Eguchi K, Niwa M.
Title A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor.
Journal J Immunol
Abstract In this work we report a novel method to efficiently induce a murine model of Graves' hyperthyroidism. Inbred mice of different strains were immunized by i.m. injection with adenovirus expressing thyrotropin receptor (TSHR) or beta-galactosidase (1 x 10(11) particles/mouse, three times at 3-wk intervals) and followed up to 8 wk after the third immunization. Fifty-five percent of female and 33% of male BALB/c (H-2(d)) and 25% of female C57BL/6 (H-2(b)) mice developed Graves'-like hyperthyroidism with elevated serum thyroxine (T(4)) levels and positive anti-TSHR autoantibodies with thyroid-stimulating Ig (TSI) and TSH-binding inhibiting Ig (TBII) activities. In contrast, none of female CBA/J (H-2(k)), DBA/1J (H-2(q)), or SJL/J (H-2(s)) mice developed Graves' hyperthyroidism or anti-TSHR autoantibodies except SJL/J, which showed strong TBII activities. There was a significant positive correlation between TSI values and T(4) levels, but the correlations between T(4) and TBII and between TSI and TBII were very weak. TSI activities in sera from hyperthyroid mice measured with some chimeric TSH/lutropin receptors suggested that their epitope(s) on TSHR appeared similar to those in patients with Graves' disease. The thyroid glands from hyperthyroid mice displayed diffuse enlargement with hypertrophy and hypercellularity of follicular epithelia with occasional protrusion into the follicular lumen, characteristics of Graves' hyperthyroidism. Decreased amounts of colloid were also observed. However, there was no inflammatory cell infiltration. Furthermore, extraocular muscles from hyperthyroid mice were normal. Thus, the highly efficient means that we now report to induce Graves' hyperthyroidism in mice will be very useful for studying the pathogenesis of autoimmunity in Graves' disease.
Volume 168(6)
Pages 2789-94
Published 2002-3-15
DOI 10.4049/jimmunol.168.6.2789
PMID 11884447
MeSH Adenoviridae / genetics* Adenoviridae / immunology* Animals Disease Models, Animal Female Graves Disease / genetics* Graves Disease / immunology* Graves Disease / pathology Graves Disease / virology Humans Injections, Intramuscular Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred CBA Mice, Inbred DBA Plasmids / administration & dosage Plasmids / biosynthesis Plasmids / immunology Receptors, Thyrotropin / administration & dosage Receptors, Thyrotropin / biosynthesis* Receptors, Thyrotropin / genetics* Thyroid Gland / pathology Vaccines, DNA / administration & dosage Vaccines, DNA / immunology Viral Vaccines / administration & dosage Viral Vaccines / immunology
IF 4.886
Times Cited 152
DNA material pCAhMCSF (RDB01524) pCM-hGM (RDB01687)