2002 Fiscal Year Final Research Report Summary
Analyses of ENU-induced brain tumors in p53 knockout mice
| Project/Area Number |
13470049
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
ODA Hideaki Tokyo Women's Medical University, a medical school, Professor, 医学部, 教授 (40214142)
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| Project Period (FY) |
2001 – 2002
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| Keywords | p53 / Knockout mice / Brain tumor / ENU / 化学発癌 |
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| Research Abstract |
We have established a brain tumor model using p53-deficient mice with ENU administration. To investigate the mechanism occurring brain tumor using this model focusing on 1) mouse, 2) cellular and 3) molecular levels.
1) Mouse level research : To clarify the relation between the stages of mouse brain development and the occurrence of brain tumors, we administered ENU in the whole stage of gestation and after birth. Early exposure to ENU showed high incidence of fetal death. During getational days from 10 to before birth, glioblastomas in the cerebrum were developed at the peak of the gestational day of 12. After birth to 1 week, medulloblastomas in cerebellum were observed at the peak of the 5 days after birth. These peak incidence of brain tumors was closely correlated with proliferation of the each brain portion and p53-dependent apoptosis after ENU administration.
2) Celluar level research : Using tumors developed in this system, we established several mouse brain tumor cell lines, which are quite rare. Among them glioblastomas, medulloblastomas and schwannomas are included. Interestingly glioblastoma and medulloblastoma cell lines have p53-null background, however, schwannoma cell lines are p53-independent. These cell lines believe to be useful for investigate the mechanisms on p53-dependent and independent brain tumors.
3) Molecular level research : We performed differential display analysis using p53 null and wild type brains after ENU administration at the gestational day of 12. So far 20 clones, which showed marked increase or suppression dependent of the genotypes were identified. After computer search, these clones were largely identified as genes related to the early mouse development, cell cycles and proliferations. Among them, Spo11 was identified to be close relation to glioblastoma occurrence. We investigate now the relation between p53 and spo11, and other genes related to cell cycle and proliferation and spo11.
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