Creation of Transgenic Mice of Dialysis-Related Amyloidosis

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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.