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

抗肾癌小鼠模型的产生及应用

• 批准号: 08557089
• 负责人: MIURA Naoyuki
• 金额: $ 7.36万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557089/
• 关键词: TORANSGENIC MICE; CHEMICAL CARCINOGENESIS; RB PROTEN; KIDNEY CANCER; LIVER CANCER; TRANSGENE; HNF1; トランスジェニックス; 腎臓; 肝臓; 肝切除; 癌抑制性遺伝子; Rb遺伝子; 腎臓癌

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.

我们已经生成了HNF1 -RB转基因小鼠，其中人Rb cDNA受HNF1（肝细胞裸子因子1）启动子的9KBP调节。与野生小鼠相比，它们没有明显的差异，可以将转基因传输到其后代。 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苯巴比妥肝癌发生8个月。对照小鼠发展了肾癌和肝癌。 RB转基因小鼠A和B线B没有出现肝癌，并且显示出比对照小鼠的结节数少，但是，RB转基因小鼠会像对照小鼠一样频繁地发展肾癌。为了解释RB转基因的影响之间的差异，我们使用共同注射的FNF1 -LACZ基因研究了RB Trausgene的表达模式。结果表明，RB转基因在所有肝细胞中均表达，但在少数肾小管细胞中均表达。表达谱与对化学癌变的抗性非常一致。

项目成果

Furumoto,T.: "Notochordo dependent expression of MFH-1 and Pax-1 cooperates to maintain the proliferation of sclerotome during the vertebral column development." Dev.Biol.(印刷中).

Furumoto, T.：“MFH-1 和 Pax-1 的脊索依赖性表达协同维持椎骨发育过程中的增殖。”Dev.Biol。

Furumoto, T.: "Notochordo dependent expression of MFH-1 and Pax-1 cooperates to maintain the proliferation of sclerotome during the vertebral column development." Dev.Biol.印刷中.

Furumoto, T.：“MFH-1 和 Pax-1 的脊索依赖性表达协同维持椎骨发育过程中的增殖。”Dev.Biol。

Kuhara,M.: "Enhancing effect of a congenital disorder in methionine metabolism on the development of spontaneous hepatitis and hepatoma in LEC rats." J.Trace Elem.Exp.Med.(in press).

Kuhara,M.：“蛋氨酸代谢先天性疾病对 LEC 大鼠自发性肝炎和肝癌发展的增强作用。”

Miura,N.: "Isolation of the mouse (MFH-1) and human (FKHL14) Mesenchyme Fork Head-1 genes reveals conservation of their gene and protein structures." Genomics. 41. 489-492 (1997)

Miura,N.：“小鼠 (MFH-1) 和人类 (FKHL14) Mesenchyme Fork Head-1 基因的分离揭示了它们基因和蛋白质结构的保守性。”

三浦直行: "ノックアウトマウス・データブック" 中山書店, 564 (1997)

三浦直之：《Knockout Mouse Data Book》中山书店，564（1997）