International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

D9. Possible Use of Somatic and Germ-Line Mutation Induced by Heavy Ion Beam(HIB) Irradiation in Mouse Carcinogenesis Models

Hiroki Nagase1, Atsushi Yoshiki2, Chikako Yoshida-Noro2 and Moriaki Kusakabe2
Molecular Oncology1, Experimental Animal Research Division2, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tukuba-shi, Ibaraki, 305-0074 Japan

The paradigm of mutation induction in cancer model is mainly used chemicals, irradiation and the other genetic manipulations, which introduce mutations in somatic and germ cells. These mutations cause susceptibility of cancer development in variety of organs of model animals. Although targeted mutagenesis has had a central role in the discovery of complex biological pathways, in order to identify novel genetic events causing complex phenotypes such as cancer susceptibility, random mutagenesis methods are being extensively developed. ENU mutagenesis reveals alternative ways to identify genetic events involved in complex phenotype introducing a single nucleotide mutation in mice at a high frequency (0.0015 per locus per gamete). Since ENU induce point mutation and have favorite nucleotide alterations, created mouse phenotype caused by the mutation may have a bias. Alternative mutagenesis must be necessary to be compensated for the bias of this method. Although availability of HIB irradiation is very restricted, several potential advantages to use this methodology to induce mutation are expected. Carcinogenic ability is confirmed likewise those of X-irradiation in mouse. Variety of mutations, including point mutation, translocation and small deletion, has been induced. Unique phenotypes that have never created by chemicals and the other irradiation are introduced in the other organisms. We are now investigating feasibility to use this method to survey correlation among mutations and phenotype effectively. Hence, an appropriate mutagenic, non-toxic dose of each heavy ion beam for strains, organs and target cells including ES cells, and their ability to recover survival or fertility are being analyzed. Frequency and types of germ-line and somatic mutation in mice will also be estimated. This relatively new mutagenic resource will be employed as a new functional genomic approach to identify genetic events in cancer susceptibility and a number of mutant mice created after treatment of HIB irradiation will be a new resource in community.

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