Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers

Geurts, A. M., Collier, L. S., Geurts, J. L., Oseth, L. L., Bell, M. L., Mu, David, Lucito, R., Godbout, S. A., Green, L. E., Lowe, S. W., Hirsch, B. A., Leinwand, L. A., Largaespada, D. A. (2006) Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PLoS Genetics, 2 (9). pp. 1413-1423. ISSN 15537390

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URL: http://www.ncbi.nlm.nih.gov/pubmed/17009875
DOI: 10.1371/journal.pgen.0020156

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. © 2006 Geurts et al.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell

organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations > mutagenesis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons
CSHL Authors:
Communities: CSHL labs > Lowe lab
CSHL labs > Lucito lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 19 Dec 2011 15:51
Last Modified: 01 Mar 2013 17:05
PMCID: PMC1584263
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22796

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