Pettersson A, Wilson D, Daniels T, Tobin S, Jacob H J, Lander E S, Lernmark A
Karolinska Institute, Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
J Autoimmun. 1995 Aug;8(4):493-505. doi: 10.1016/0896-8411(95)90004-7.
The spontaneously diabetic BB rat is an excellent and well studied model for human insulin-dependent diabetes (IDDM), sharing many important features with the human disease. Similarities include an equal frequency of IDDM in males and females, production of antibodies against pancreatic cell antigens, and an MHC disease association. In addition, the BB rat shares with human IDDM patients an increased frequency of autoantibodies against the parietal cells of the stomach and colloid cells of the thyroid gland. Here we investigate the genetic basis of thyroiditis in the BB rat. Based on crosses between BB, Lewis and Fischer rats, we show that two susceptibility factors for diabetes--the lymphopenia trait present in diabetes prone BB rats and the MHC--also appear to be risk factors for thyroiditis. However, the nature of the susceptibility was different for the two autoimmune diseases, with lymphopenia being absolutely required for diabetes although it only conferred increased risk for thyroiditis. Also, in contrast to IDDM, the MHC conferred dominant susceptibility to thyroiditis. Despite these shared risk factors, diabetes per se did not show significant correlation with thyroiditis.
自发性糖尿病BB大鼠是一种用于研究人类胰岛素依赖型糖尿病(IDDM)的优秀且研究充分的模型,它与人类疾病具有许多重要特征。相似之处包括男性和女性IDDM的发病频率相同、产生针对胰腺细胞抗原的抗体以及MHC疾病关联。此外,BB大鼠与人类IDDM患者一样,针对胃壁细胞和甲状腺胶质细胞的自身抗体频率增加。在此,我们研究BB大鼠甲状腺炎的遗传基础。基于BB、Lewis和Fischer大鼠之间的杂交,我们发现糖尿病的两个易感性因素——糖尿病易感BB大鼠中存在的淋巴细胞减少特征和MHC——似乎也是甲状腺炎的风险因素。然而,这两种自身免疫性疾病的易感性性质不同,淋巴细胞减少是糖尿病绝对必需的,尽管它只是增加了甲状腺炎的风险。此外,与IDDM相反,MHC赋予了对甲状腺炎的显性易感性。尽管存在这些共同的风险因素,但糖尿病本身与甲状腺炎并未显示出显著相关性。