1998 Fiscal Year Final Research Report Summary
GENERATION AND APPLICATION OF THE MODEL MICE WHICH SHOW RESISTANCE TO RENAL CARCINOGENESIS
| Project/Area Number |
08557089
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Urology
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| Research Institution | AKITA UNIVERSITY |
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Principal Investigator |
MIURA Naoyuki AKITA UNIV,SCH MED,ASSOC PROF, 医学部, 助教授 (40165965)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Nobuaki UNIV TOKYO,INST MED SCI,PROF, 医科学研究所, 教授 (10250341)
TERADA Kunihiko AKITA UNIV,SCH MED,ASSIST PROF, 医学部, 講師 (60197796)
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| Project Period (FY) |
1996 – 1998
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| Keywords | TORANSGENIC MICE / CHEMICAL CARCINOGENESIS / RB PROTEN / KIDNEY CANCER / LIVER CANCER / TRANSGENE / HNF1 |
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| Research Abstract |
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.
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[Publications] Yasui, O., Miura, N., Terada, K., Kawarada, Y., Koyama, K., and Sugiyama, T.: "Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver." Hepatoloty. 25. 329-334 (1997)
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[Publications] Iida, K., Koseki, H., Kakinuma, H., Kato, N., Mizutani-Koseki, Y., Ohuchi, H., Yoshioka, H., Noji, S., Kawamura, K., Kataoka, Y., Ueno, F., Taniguchi, M., Yoshida, N., Sugiyama, T., and Miura, N.: "Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis." Development. 124. 4627-4638 (1997)
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[Publications] Terada, K., Nakako, T., Yang, X-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., and Sugiyama, T.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA" J.Biol.Chem.273. 1815-1820 (1998)
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[Publications] Furumoto, T., Miura, N., Akasaka, T., Mizutani-Koseki, Y., Sudo, H., Fukuda, K., Maekawa, M., Yuasa, S., Fu, Y., Moriya, H., Taniguchi, M., Imai, K., Dahl, E., Balling, R., Pavlova, M., Gossler, A., and Koseki, H.: "Notochordo dependent expression of MFH-1 and Pax-1 cooperates to maintain the proliferation of sclerotome during the vertebral column development." Dev.Biol.(in press).
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