GENERATION AND APPLICATION OF THE MODEL MICE WHICH SHOW RESISTANCE TO RENAL CARCINOGENESIS

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We have generated the HNF1 -Rb transgenic mice in which the human Rb CDNA is regulated under the 9kbp of HNF1 (hepatocyte nudear factor 1) promoter. They showed no apparent differences compared to the wild mice and they can transmit the transgene to their offspring. The numbers of the Rb transgene were 11.0 copies per haploid for line A and 4.2 copies per haploid for line B.The weights of kidney and liver in the Rb transgenic mice were not different from the control mice.Next we treated the mice with Iron Nitrotriacetate intraperitoneally for 3 months for kidney carcinogenesis and with diethylnitrosamine intraperitoneally and phenobarbital orally for 8 months for liver carcinogenesis. Control mice developed kidney carcinomas and liver carcinomas. The Rb transgenic mice, line A and line B, did not develop liver carcinoma and also showed smaller number of nodules than control mice, However, the Rb transgenic mice develop kidney carcinomas as frequently as control mice. In order to explain the differences between the effects of Rb transgene, we investigated the expression pattern of the Rb trausgene using the coinjected FNF1 -LacZ gene. The results showed that the Rb transgene was expressed in all hepatocytes, but in a small number of renal tubular cells. The expression profile is in good consistency with the resistance to chemical carcinogenesis.