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Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PLoS Genet 2006 Sep 29;2(9):e156

Date

10/03/2006

Pubmed ID

17009875

Pubmed Central ID

PMC1584263

DOI

10.1371/journal.pgen.0020156

Scopus ID

2-s2.0-33749416026   74 Citations

Abstract

Previous studies of the Sleeping Beauty (SB) transposon system, as an insertional mutagen in the germline of mice, have used reverse genetic approaches. These studies have led to its proposed use for regional saturation mutagenesis by taking a forward-genetic approach. Thus, we used the SB system to mutate a region of mouse Chromosome 11 in a forward-genetic screen for recessive lethal and viable phenotypes. This work represents the first reported use of an insertional mutagen in a phenotype-driven approach. The phenotype-driven approach was successful in both recovering visible and behavioral mutants, including dominant limb and recessive behavioral phenotypes, and allowing for the rapid identification of candidate gene disruptions. In addition, a high frequency of recessive lethal mutations arose as a result of genomic rearrangements near the site of transposition, resulting from transposon mobilization. The results suggest that the SB system could be used in a forward-genetic approach to recover interesting phenotypes, but that local chromosomal rearrangements should be anticipated in conjunction with single-copy, local transposon insertions in chromosomes. Additionally, these mice may serve as a model for chromosome rearrangements caused by transposable elements during the evolution of vertebrate genomes.

Author List

Geurts AM, Collier LS, Geurts JL, Oseth LL, Bell ML, Mu D, Lucito R, Godbout SA, Green LE, Lowe SW, Hirsch BA, Leinwand LA, Largaespada DA

Authors

Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Jennifer L. Geurts MS, CGC Director, Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Chromosome Aberrations
Chromosomes
Chromosomes, Mammalian
Crosses, Genetic
DNA Transposable Elements
DNA, Concatenated
Genes, Dominant
Genes, Recessive
Mice
Mice, Transgenic
Models, Biological
Mutagenesis, Insertional
Mutation
Pedigree
Phenotype
Syndactyly
Transposases