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Publication : Identification of radiation-responsive genes in vitro using a gene trap strategy predicts for modulation of expression by radiation in vivo.

First Author  Vallis KA Year  2002
Journal  Radiat Res Volume  157
Issue  1 Pages  8-18
PubMed ID  11754636 Mgi Jnum  J:197093
Mgi Id  MGI:5490782 Doi  10.1667/0033-7587(2002)157[0008:iorrgi]2.0.co;2
Citation  Vallis KA, et al. (2002) Identification of radiation-responsive genes in vitro using a gene trap strategy predicts for modulation of expression by radiation in vivo. Radiat Res 157(1):8-18
abstractText  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.
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