Fine mapping of radiation susceptibility and gene expression analysis of LEC congenic rat lines.
LEC rats constitute an animal model of high susceptibility to X-rays. We developed congenic LEC rat lines (recipient strain, Fischer 344 (F344)) and performed genome-wide genotyping to identify radiation susceptibility genes. We mapped seven positional candidate genes, Bmp10, Gpr73, Gp9, Cnbp, Copg, Rab7, and Rpn1, to an approximately 1.2-Mb region located between loci D4Got85 and D4Got148 on chromosome 4. None of the seven genes has been reported to be associated with radiation susceptibility. Comparison of the coding sequences for these seven genes in F344 and LEC rats showed no changes in deduced amino acid sequences. We determined gene expression differences in Gp73, Gp9, and Cnbp as well as strain-specific variations in upstream sequences of these genes. Our results suggest that radiation susceptibility in the LEC rat is primarily attributable to one of the genes within this approximately 1.2-Mb region; however, expression analysis gave no clear indication as to which gene is responsible.
Tsuji
Atsushi B
AB
RadGenomics Project, Frontier Research Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Sugyo
Aya
A
Ogiu
Toshiaki
T
Sagara
Masashi
M
Kimura
Tomo
T
Ishikawa
Atsuko
A
Sudo
Hitomi
H
Ohtsuki
Marika
M
Aburatani
Hiroyuki
H
Imai
Takashi
T
Harada
Yoshi-Nobu
YN
D000818:Animals; D020296:Animals, Congenic / Q000235:genetics*; D002874:Chromosome Mapping; D015870:Gene Expression; D011836:Radiation Tolerance / Q000235:genetics*; D051381:Rats; D020332:Rats, Inbred LEC / Q000235:genetics*; D014965:X-Rays