Generation of new model mice for brain tumors usuing conditional knockout method

2014 Fiscal Year Final Research Report

• Project/Area Number: 23592115
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Niigata University
• Principal Investigator: USUI Hiroshi 新潟大学, 脳研究所, 非常勤講師 (20192510)
• Co-Investigator(Kenkyū-buntansha): SAKIMURA Kenji 新潟大学, 脳研究所, 教授 (40162325) ; WASHIYAMA Kazuo 新潟大学, 脳研究所, 准教授 (00183715)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 脳腫瘍 / モデルマウス / 癌抑制遺伝子 / 細胞選択的機能破壊

Outline of Final Research Achievements

In order to generate novel model mice for brain tumors, we produced Trp53 gene-knockout and Nf1 gene-conditional knockout mice, in which Trp53 gene was deleted in the whole body and Nf1 gene was destroyed specifically in the brain cells. For this purpose, Trp53-null/Nf1-flox mice were crossed with 3 types of Cre-knock in mice where Cre recombinase were expressed in the brain-specific manner (Nestin-Cre, GFAP-Cre, and NG2-Cre mice). Most of the resulting mice died by 9 months-old and expressed brain tumors in high frequency. Among them, when Trp53-null/Nf1-flox mice were crossed with the NG2-Cre mice in which Cre recombinase was expressed in NG2 glial cells (oligodendroglia progenitor cells), 89% (32/36) of mice exhibited brain tumors, most of which were oligodendrogliomas or anaplastic oligodendrogliomas. Our results showed that the model mice of brain tumors were efficiently produced by the conditional knockout method.

Free Research Field

分子神経病理学