Creation of Transgenic Mice of Dialysis-Related Amyloidosis

为了阐明透析相关淀粉样变性的发病机制和建立治疗方法，我们采用RT-PCR方法克隆了人β_2-M基因，将其插入pCAGGS的XhoI位点，建立了过量表达人β_2-M基因的转基因小鼠（F0 5株）。用RT-PCR和北方印迹法检测人β_2-MmRNA，用Western印迹法检测人血清和尿β_2-M。我们通过交配F1产生纯合子转基因小鼠。人血β_2-M水平（20- 30 mg/l）与血液透析患者相当。我们在转基因小鼠中未观察到透析相关的淀粉样变性。这些结果表明，只有高β_2-M不能引起透析相关性淀粉样变性。我们观察透析相关性淀粉样变患者慢性肾功能衰竭。为了增加透析相关淀粉样变性发展的一个关键因素，慢性肾衰竭，我们制造了六分之五肾切除的转基因小鼠。我们将分析这些老鼠。

To clarify the pathogenesis and establish therapy of dialysis-related amyloidosis, , we cloned humanβ_2-M cDNA by RT-PCR.We inserted humanβ_2-M cDNA into unique XhoI site of pCAGGS.We generated transgenic mice overexpressing humanβ_2-M (F0 5 lines). We confirmed humanβ_2-MmRNA by RT-PCR and northern blotting analysis, serum and urine humanβ_2-M by western blotting. We generated homozygote transgenic mice by mating F1. Serum humanβ_2-M levels (20-30mg/l)were as high as those levels in hemodialyzed patients. We could not observe dialysis-related amyloidosis in transgenic mice. These results demonstrated that only hyper β_2-M could not cause dialysis-related amyloidosis. We observe dialysis-related amyloidosis patients with chronic renal failure. To add a crucial factor, chronic renal failure, for development of dialysisrelated amyloidosis, we created five-sixths nephrectomized transgenic mice. We will analyze these mice.