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A large number of genes are known to be responsive to ionizing radiation, and there is strong evidence for the existence of inducible radiation resistance in mammalian cells. We have developed a gene trap insertional mutagenesis strategy to identify novel genes involved in responses to radiation. Using this approach, we have isolated four gene-trap integrations in embryonic stem cells. In three cases (9A, 3E and 9H) the trapped genes are radiation-inducible, and in one (7D) the gene is down-regulated. Sequence analysis of fusion transcripts from three of the integrations indicate one novel gene (3E), the mouse homologue (9A) of a known but uncharacterized human gene that encodes a protein with significant homology to several GTPase-activating proteins and a murine locus, Mym (9H). The embryonic stem cell clone with the 9A insertion was introduced into the mouse germline, and the in vivo expression pattern of 9A was studied in detail. A unique, spatially restricted pattern of expression in embryos and adult animals was observed. There is tissue-specific in vivo induction of the 9A gene in adult mice by radiation. This study demonstrates the potential of the gene trap approach for the identification and functional analysis of novel radiation-regulated genes. Similar strategies may facilitate the discovery and characterization of genes involved in other cellular stress responses.

Type

Journal article

Journal

Radiat Res

Publication Date

01/2002

Volume

157

Pages

8 - 18

Keywords

Amino Acid Sequence, Animals, Chimera, Clone Cells, Coculture Techniques, DNA Damage, Embryo Transfer, Embryo, Mammalian, Expressed Sequence Tags, Female, Fetal Proteins, Gene Expression Regulation, Genes, Genes, Reporter, Genetic Vectors, Germ-Line Mutation, Humans, Introns, Lac Operon, Male, Mice, Mice, Knockout, Molecular Sequence Data, Mutagenesis, Insertional, Polymerase Chain Reaction, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Stem Cells, beta-Galactosidase