Mordes John P, Guberski Dennis L, Leif Jean H, Woda Bruce A, Flanagan Joan F, Greiner Dale L, Kislauskis Edward H, Tirabassi Rebecca S
BioMedical Research Models, 67 Millbrook St., Suite 422, Worcester, MA 01606, USA.
Diabetes. 2005 Sep;54(9):2727-33. doi: 10.2337/diabetes.54.9.2727.
We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1(u/u/a)) occurs with a cumulative frequency of approximately 2% at a median age of 59 days. The disease is characterized by hyperglycemia, glycosuria, ketonuria, and polyuria. Both sexes are affected, and islets of acutely diabetic rats are devoid of beta-cells, whereas alpha- and delta-cell populations are spared. The peripheral lymphoid phenotype is normal, including the fraction of ART2(+) regulatory T-cells. We tested the hypothesis that the expression of diabetes would be increased by immunological perturbation of innate or adaptive immunity. Treatment of young rats with depleting anti-ART2.1 monoclonal antibody increased the frequency of diabetes to 50%. Treatment with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100%. All diabetic rats exhibited end-stage islets. The LEW.1WR1 rat is also susceptible to collagen-induced arthritis but is free of spontaneous thyroiditis. The LEW.1WR1 rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation.
我们描述了一种在主要组织相容性复合体同源LEW大鼠中出现的自身免疫性糖尿病新大鼠模型。LEW.1WR1大鼠（RT1(u/u/a)）的自发性糖尿病在中位年龄59天时累计发生率约为2%。该疾病的特征为高血糖、糖尿、酮尿和多尿。两性均受影响，急性糖尿病大鼠的胰岛缺乏β细胞，而α细胞和δ细胞群体未受影响。外周淋巴细胞表型正常，包括ART2(+)调节性T细胞的比例。我们检验了一个假设，即先天性或适应性免疫的免疫扰动会增加糖尿病的发生率。用消耗性抗ART2.1单克隆抗体治疗幼鼠可使糖尿病发生率增加至50%。用Toll样受体3配体聚肌苷酸:聚胞苷酸治疗可使糖尿病发生率增加至100%。所有糖尿病大鼠均表现为终末期胰岛。LEW.1WR1大鼠也易患胶原诱导的关节炎，但无自发性甲状腺炎。LEW.1WR1大鼠为研究在遗传上易患这两种疾病且可因环境扰动而加重的动物中的自身免疫性糖尿病和关节炎提供了一种新模型。
