Region-specific saturation germline mutagenesis in mice using the Sleeping Beauty transposon system.
Recent consolidation of the whole-genome sequence with genome-wide transcriptome profiling revealed the existence of functional units within the genome in specific chromosomal regions, as seen in the coordinated expression of gene clusters and colocalization of functionally related genes. An efficient region-specific mutagenesis screen would greatly facilitate research in addressing the importance of these clusters. Here we use the 'local hopping' phenomenon of a DNA-type transposon, Sleeping Beauty (SB), for region-specific saturation mutagenesis. A transgenic mouse containing both transposon (acts as a mutagen) and transposase (recognizes and mobilizes the transposon) was bred for germ-cell transposition events, allowing us to generate many mutant mice. All genes within a 4-Mb region of the original donor site were mutated by SB, indicating the potential of this system for functional genomic studies within a specific chromosomal region.
Keng
Vincent W
VW
Center for Advanced Science and Innovation, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yae
Kojiro
K
Hayakawa
Tomoko
T
Mizuno
Sumi
S
Uno
Yoshihiro
Y
Yusa
Kosuke
K
Kokubu
Chikara
C
Kinoshita
Taroh
T
Akagi
Keiko
K
Jenkins
Nancy A
NA
Copeland
Neal G
NG
Horie
Kyoji
K
Takeda
Junji
J
D000818:Animals; D004251:DNA Transposable Elements / Q000235:genetics*; D018390:Gene Targeting / Q000379:methods*; D018095:Germ-Line Mutation; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D005810:Multigene Family; D016254:Mutagenesis, Insertional / Q000379:methods*
D004251:DNA Transposable Elements