Model of the athymic nude mouse for the study of benign goiter disease

Abstract

Since Shimosato et al., in the mid 70s transplanted for the first time thyroid carcinoma tissue onto nude mice, other research groups have made use of the nude mouse model for the investigation of xenotransplanted thyroid tissue. The use of this model for the investigation of benign goiters is briefly discussed in this article. Normal human thyroid tissue has been transplanted either as a control in experiments with benign and malignant goiter tissue, or for the study of thyroid tissue response to stimulators such as TSH or thyroid stimulating antibodies (TSAb). Thyroid glands from 8- to 10-week old human fetuses obtained at the time of legal abortion were cryopreserved in liquid nitrogen and successfully transplanted into nude mice. Moreover, all the variants of human benign goiter tissue have been xenotransplanted: tissue from nodular and diffuse goiters, hot and cold nodules or goiter areas, rapidly growing nodules, etc. Two examples of animal thyroid tissue xenotransplantation onto nude mice are briefly discussed: Nude mice bearing normal thyroid tissue transplants from 4 different species (man, rat, pig, guinea-pig) have been used for the study of the species specific effect of bovine TSH and TSAb. In studies aiming at elucidating the pathogenesis of hyperthyroidism, toxic goiter tissue from hyperthyroid cats has been transplanted. In methodological terms, these experiments have shown that surgically removed goiter tissue can be shipped by air in cell culture medium at 4 degrees C over long distances and then successfully transplanted.-Finally, cell lines such as the rat cell line FRTL-5 can be transplanted onto nude mice either as cell suspension or embedded in collagen, for example for the study of proliferation and folliculogenesis. Using the xenotransplantation model, function and proliferation, morphogenesis and differentiation, as well as thyroid autonomy and response to stimulators have all been studied in xenotransplanted human and animal thyroid thyroid tissue and cell lines under various experimental conditions. Although new research tools, for example transgenic animals, are now increasingly and successfully used, xenotransplantation still offers the possibility of addressing some specific questions which cannot be answered so easily with other experimental models. For example, studies with human tissue, involving drugs or radioactive tracers which cannot be applied to the intact human being, can relatively easily be performed with xenotransplanted human tissue and application of the drug or tracer to the host mouse. Or embryological development can be followed and studied using fetal thyroid (and other) tissue transplanted onto nude mice; here, of course, difficult ethical issues have to be considered. Finally, it should be mentioned that, although many scientific questions can be studied nowadays by cell culture or other in vitro systems, animal models are still needed. Extrapolation to the human being, however, should always be done with caution and we should always keep in mind that for the understanding of a human disease indeed human experimental models remain the goldstandard.