INDUCTION OF HYPERTHYROXINEMIA IN BALB C BUT NOT IN SEVERAL OTHER STRAINS OF MICE/

We recently expressed the extracellular domain of the human TSHR (ETSH R) protein using a baculovirus expression system and purified it to ho mogeneity. The ETSHR specifically binds both TSH and antibodies to TSH R. In the present study, C57BL/6J, SJL/J, BALB/cJ and B10BR.SgSnJ mice were immunized with the recombinant ETSHR or an equivalent amount of control antigen. All strains of mice produced high titers of antibody against the TSHR protein which were capable of blocking the binding of TSH to native TSHR. However, only BALB/cJ mice showed significantly e levated levels of thyroxine in their sera compared to the control mice . Similarly. BALB/cJ mice primed with ETSHR and then challenged with t hyroid membranes showed significantly elevated levels of thyroxine. In addition, histopathological examination of thyroid glands from affect ed mice showed morphological changes characterized by hydropic and sub nuclear vacuolar changes and focal scalloping, with no apparent inflam mation or glandular destruction. Moreover, mice with elevated thyroxin e levels showed increased in vivo thyroidal uptake of (131)Iodine. Tog ether, these data suggest that BALB/cJ mice are susceptible to the ind uction of hyperthyroxinemia.