@misc{oai:repo.qst.go.jp:00067454,
 author = {Kakinuma, Shizuko and Nishimura, Mayumi and Kubo, Ayumi and Nagai, Junya and Ogiu, Toshiaki and Majima, Hideyuki and Sado, Toshihiko and Shimada, Yoshiya and 柿沼 志津子 and 西村 まゆみ and 久保 歩 and 永井 絢也 and 荻生 俊昭 and 馬嶋 秀行 and 佐渡 敏彦 and 島田 義也},
 month = {Aug},
 note = {Ikaros is a Kruppel-type zinc-finger transcription factor that plays a critical role in both lineage commitment and differentiation of lymphocytic leukemia. We previously reported, in the X-ray-induced T-cell leukemia (TL) in B6C3F1 mice, a unique locus with high frequency of loss of heterozygosity (LOH) in centromeric region of chromosome 11, and mapped the Ikaros gene in this locus. In contrast, LOH at Ikaros locus was rarely observed in ENU-induced TL. The aim of our study was to compare molecular alteration of Ikaros gene between X-ray-induced and ENU-induced TL.
For induction of TL, the mice were exposed weekly to 1.6 Gy whole body X-irradiation for 4 consecutive weeks or were given (ENU; 400 ppm) in drinking water for consecutive 6 weeks. DNA and total RNA were extracted from primary TL. LOH status at Ikaros locus, expression status and genetic changes of Ikaros was determined using RT-PCR, Western Blotting and nucleotide sequencing. Subcellar localization of Ikaros in the TL cells was also analyzed.
The results indicated, in X-ray induced TL, Ikaros was inactivated by multiple mechanisms (null expression, expression of dominant negative isoforms and creation of point mutation). In contrast, ENU-induced TL showed predominantly point mutation. The point mutations in both-type tumors were similar in the frequencies, but differ in spectrum. The point mutation was frequently accompanied by the existence of LOH at Ikaros locus in X-ray-induced TL, while it was not in ENU-induced TL. These results suggest that the mechanism of Ikaros inactivation is different between X-ray-induced and ENU-induced TL., International Congress of Radiation Research},
 title = {Diverse Mechanism in Mutation of Ikaros Gene in Murine T-cell Leukemia Induced by Radiation or N-Ethyl-N-Nitrosourea in B6C3F1 Mice.},
 year = {2003}
}