@misc{oai:repo.qst.go.jp:00067457, author = {Tsuji, Atsushi and Sugyou, Aya and Sagara, Masashi and Suga, Tomo and Ishikawa, Atsuko and Ogiu, Toshiaki and Imai, Takashi and Harada, Yoshinobu and 辻 厚至 and 須尭 綾 and 相良 雅史 and 菅 智 and 石川 敦子 and 荻生 俊昭 and 今井 高志 and 原田 良信}, month = {Aug}, note = {Even if the human genome has been sequenced completely, it is difficult to determine the genes associated with the complicated radiation-induced responses in human. Therefore, the genetic analysis of an appropriate animal model is a useful approach to gain understanding of radiation-induced responses. A LEC rat is known to be an animal model of highly susceptibility to X-ray irradiation characterized by intestinal death, bone marrow death and impaired DNA repair. In order to identify the radiation susceptibility gene in the LEC rat, congenic rat lines developed by introgressing a LEC chromosomal segment into a F344 background using a phenotype-driven breeding protocol, and we performed a genome-wide genotyping of congenic rats and their progeny for selection tests. We determined that the susceptibility gene for X-irradiation was located in the chromosomal region on rat chromosome 4. In order to construct a high-resolution map, we mapped 30 microsatellite markers, four known genes and 73 ESTs using rat radiation hybrid panel. Then, we constructed a BAC contig in the chromosomal region using hybridization and PCR, and we estimate that a physical distance could be approximately 1Mb using pulse-field gel electrophoresis. We performed the sequencing of four positional candidate genes, and we determined no mutation causing amino acid substitution in their coding sequences between LEC and F344 rats. In addition, we could not find other candidate genes in the conserved chromosomal regions on human chromosome 3q21 and mouse chromosome 6. These findings suggest that the radiation susceptibility gene in the LEC rat would be a novel gene. Therefore, the determination of the radiation susceptibility gene for the LEC rat will be helpful to understand the molecular mechanism of irradiation-induced response in human., The 12th International Congress of Radiation Research(ICRR)}, title = {Construction of high-resolution and physical maps around a radiation susceptibility gene on rat chromosome 4 using LEC congenic lines}, year = {2003} }