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

我们培育了HNF1 -Rb转基因小鼠，其中人Rb CDNA受HNF1（肝细胞核因子1）启动子9kbp的调控。与野生小鼠相比，它们没有表现出明显的差异，而且它们可以将转基因基因传给后代。转Rb基因A系为11.0个拷贝/单倍体，转Rb基因b系为4.2个拷贝/单倍体，转Rb基因小鼠的肾脏和肝脏重量与对照小鼠无显著差异。接下来，我们用三醋酸氮铁腹腔治疗肾癌3个月，用二乙基亚硝胺腹腔和苯巴比妥口服治疗肝癌8个月。对照组小鼠出现肾癌和肝癌。Rb转基因小鼠A系和B系未发生肝癌，结节数量也少于对照小鼠，而Rb转基因小鼠发生肾癌的频率与对照小鼠相同。为了解释Rb转基因效果的差异，我们使用共注射FNF1 -LacZ基因来研究Rb转基因的表达模式。结果表明，Rb基因在所有肝细胞中均有表达，但在少量肾小管细胞中均有表达。其表达谱与抗化学致癌具有良好的一致性。

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.