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Development of the gene deletion model rats by random mutagenesis

Research Project

Project/Area Number 14580805
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

HARADA Yoshinobu  National Institute of Radiological Sciences, Frontier Research Center, Researcher, フロンティア研究センター, 研究員 (90192707)

Co-Investigator(Kenkyū-buntansha) TSUJI Atsusi  National Institute of Radiological Sciences, Frontier Research Center, Researcher, フロンティア研究センター, 研究員 (60303559)
KITO Seiji  National Institute of Radiological Sciences, Department of technical support and development, Researcher, 基盤研究部, 研究員 (20311376)
XUE ZHI Sun  National Institute of Radiological Sciences, Research Center for Radiation Safety, Researcher, 放射線安全研究センター, 研究員 (00284323)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsrat / chlorambucil / mutagenesis / gene deletion / model animal / microarray / 突然変異 / BN / F344
Research Abstract

Random mutagenesis with chlorambucil was performed in order to produce some new mutant rats. To identify the optimal quantity of chlorambucil and the optimal mating time for mutagenesis, we counted the number of new born rats born from female rats mated with the male rat medicated with several dose of chlorambucil. Consequently, it became clear that between 5mg and 15mg per kg weight of chlorambucil are good for medication, and it is good to perform mating between three weeks and six weeks after the medication of chlorambucil. The female (G1 generation) rat was obtained as a result of crossing between the male rat of BN strain medicated with 10mg chlorambucil and a normal F344 female rat. This female rat has the capability to conceive. A male rat (G3 generation) was obtained from a cross the female rat (G2 generation) with the male rat (G3 generation). Then we crossed these rats and obtained six rats. When these six rats were bred for about one year, one of the rats had skin cancer and another one showed diabetes symptom. It was presumed that these rats are the mutants by which mutation was occurred in some genes. In addition, the dwarfish rat whose size of the body is about 30% of a normal rat was also observed. In almost all cases, the dwarfish rats died before weaning, but a few dwarfish rats grew to the adult. Although the adult dwarfish rats was able to be conceived, they born some dwarfish rats by mating with a normal rat similarly. In order to confirm to which gene mutation has happened, gene expression analysis was performed for the G5 generation rats using DNA microarray. Consequently, it was proved that at least ten kinds of genes was not expressed in the G5 rats. These genes were presumed that the expression of these genes was suppressed by deletion type of mutation in each genes.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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