Endocrine Abstracts (2002) 3 P302

Environmental factors produce variation within a model of thyroid eye disease

GRC Baker & M Ludgate

Section of Endocrinology, UWCM, Cardiff, UK.

An established murine model of thyroid eye disease is induced by transfer of thyrotropin receptor (TSHR) primed T-cells to syngeneic recipients. Our aim was to extend the model to determine if: there are gender differences, Rundle's curve occurs and magnetic resonance imaging (MRI) could be applied as an in vivo marker. Orbital MRI on non-living mice used a surface coil and 1.5T MRI. 0.75mm slices have resolution sufficient to image ocular muscles. TSHR primed T-cells were generated via fusion protein with adjuvant or genetic immunisation in anaesthetized female BALBc (Iffa Credo, supplier of those previously developing disease). At twelve weeks they were sacrificed and orbits, thyroids, spleen and blood were taken. Serum was examined for total thyroxine (T4, using a RIA), antibodies to TSHR were detected using flow cytometry and thyrotropin stimulating (TSAB) and inhibiting (TBII) antibodies were assessed by cell bioassays. Nine surviving mice developed TSHR antibodies confirmed by flow, 5/9 had TSAB activity, 4/9 had TBII and average T4 was 8.4 micrograms/100ml (euthyroid range 3-6). Histologically, thyroids and ocular muscles were normal. A transfer experiment failed to induce thyroiditis. The results are markedly different from before despite identical protocols and mice. Previously 30-60% developed thyroiditis, the majority are TBII positive, TSAB are very rare and no changes in T4 occur. To investigate possible environmental modulating factors, four groups of five female BALBc were examined. Both immunisation methods were used, groups were either maintained on local chow, water and bedding or on supplies identical to the Brussels experiments. Preliminary results indicate that TSHR antibodies can be detected by flow in all 7/7 fusion protein recipients, but in the genetically immunized, only 1/5 of the local regime and 3/5 Brussels regime mice. These differences suggest environmental factors are significant and may be linked with dietary iodine.

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