The Use of the Severe Combined Immunodeficient Mouse and the Athymic “Nude” Mouse as Models for the Study of Human Autoimmune Thyroid Disease

The athymic “nude” mouse and the severe combined immunodeficient (SCID) mouse have differing immunological properties which permit complementary studies of autoimmune thyroid disease (AITD). The nude mouse accepts human thyroid xenografts, but lyses the passenger lymphocytes, whereas in the SCID mouse both the xenograft and its lymphocytes survive. Human AITD thyroid xenografts manifest a worsening of the pathological picture in the SCID mouse, but show a return to normal morphology and function in the nude mouse at the time of sacrifice 6-8 weeks after engraftment. Such tissue which has been grafted into the nude mouse can be retrieved and then can be rexenografted into the SCID mouse. Normalized AITD thyroid tissue (from the nude mouse xenograft) will remain normal in the SCID mouse, but if xenografted into a SCID mouse which already has a primary autologous AITD thyroid xenograft, or if autologous PBMC are added, the AITD lesion will be reproduced. This demonstrates the primacy of the immune system in AITD and constitutes a useful model for the study of this human disorder.