Wang Dong, Lu Houshan, Zhang Bin, Chen Zhankun, Jiang Dongfang, Ai Jing
Arthritis Clinical and Research Center, People's Hospital, Peking University, Beijing 100044, China.
Zhonghua Wai Ke Za Zhi. 2002 Mar;40(3):216-8.
To confirm the role of HLA-B2704 and hbeta(2)m gene in the pathogenesis of spontaneous inflammatory diseases by establishing HLA-B2704 and hbeta(2)m double transgenic mice model of ankylosing spondylitis. It will provide a powerful animal model for exploring the etiology, prevention and treatment of B27-relevant diseases.
The screening, identification and expression of HLA-B2704 and hbeta(2)m gene were determined by PCR, dot blot, Southern blot hybridization, RT-PCR, flow cytometry and immunohistochemistry. HE staining was performed for the diseased mice.
Eight double transgenic mice bearing high copy developed spontaneous dermatosis, arthritis and nail changes in the rear paw. The results of flow cytometry in normal mice, B27 single transgenic mice, and HLA-B27/hbeta(2)m double transgenic mice were 0.63%, 7.87% and 35.87% respectively. HLA-B2704 antigen was high expressed on the cell surface, but not evident on those of B27 single transgenic mice.
HLA-B2704 heavy chain can induce spontaneous inflammatory diseases in the transgenic mice. Hbeta(2)m can form a stable complex with HLA-B27 and may stabilize and enhance the expression of HLA-B2704 on the cell surface.
通过建立强直性脊柱炎HLA - B2704和hβ2m双转基因小鼠模型，证实HLA - B2704和hβ2m基因在自发性炎症性疾病发病机制中的作用。为探索B27相关疾病的病因、预防和治疗提供有力的动物模型。
采用PCR、斑点杂交、Southern杂交、RT - PCR、流式细胞术和免疫组化等方法检测HLA - B2704和hβ2m基因的筛选、鉴定及表达情况。对患病小鼠进行HE染色。
8只携带高拷贝的双转基因小鼠出现自发性皮肤病、关节炎和后爪指甲改变。正常小鼠、B27单转基因小鼠和HLA - B27/hβ2m双转基因小鼠的流式细胞术检测结果分别为0.63%、7.87%和35.87%。HLA - B2704抗原在细胞表面高表达，而在B27单转基因小鼠细胞表面不明显。
HLA - B2704重链可诱导转基因小鼠发生自发性炎症性疾病。hβ2m可与HLA - B27形成稳定复合物，并可能稳定和增强HLA - B2704在细胞表面的表达。
