title: Germline translocations in mice: unique tools for analyzing gene function and long-distance regulatory mechanisms.
abstract: Translocations have provided invaluable tools for identifying both cancer-linked genes and loci associated with heritable human diseases, but heritable human translocations are rare and few mouse models exist. Here we report progress on analysis of a collection of heritable translocations generated by treatment of mice with specific chemicals or radiation during late spermatogenic stages. The translocation mutants exhibit a range of visible phenotypes reflecting the disruption of coding sequences or the separation of genes from essential regulatory elements. The breakpoints of both radiation-induced and chemically induced mutations in these mice are remarkably clean, with very short deletions, duplications, or inversions in some cases, and ligation mediated by microhomology, suggesting nonhomologous end joining as the major path of repair. These mutations provide new tools for the discovery of novel genes and regulatory elements linked to human developmental disorders and new clues to the molecular basis of human genetic disease.
authors.affiliation: Genome Biology, Lawrence Livermore National Laboratory, 7000 East Ave, L-452, Livermore CA 94550, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Elso
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Lu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Morrison
authors.forename: Angela
authors.initials: A
authors.lastname: Tarver
authors.forename: Heather
authors.initials: H
authors.lastname: Thompson
authors.forename: Hillary
authors.initials: H
authors.lastname: Thurkow
authors.forename: N Alice
authors.initials: NA
authors.lastname: Yamada
authors.forename: Lisa
authors.initials: L
authors.lastname: Stubbs
mesh_terms: D000016:Abnormalities, Radiation-Induced / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002869:Chromosome Aberrations; D030342:Genetic Diseases, Inborn / Q000139:chemically induced / Q000235:genetics*; D005854:Germ Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D014178:Translocation, Genetic