Region-specific saturation germline mutagenesis in mice using the Sleeping Beauty transposon system

作者: Vincent W Keng , Kojiro Yae , Tomoko Hayakawa , Sumi Mizuno , Yoshihiro Uno

DOI: 10.1038/NMETH795

关键词:

摘要: Recent consolidation of the whole-genome sequence with genome-wide transcriptome profiling revealed existence functional units within genome in specific chromosomal regions, as seen coordinated expression gene clusters and colocalization functionally related genes. An efficient region-specific mutagenesis screen would greatly facilitate research addressing importance these clusters. Here we use 'local hopping' phenomenon a DNA-type transposon, Sleeping Beauty (SB), for saturation mutagenesis. A transgenic mouse containing both transposon (acts mutagen) transposase (recognizes mobilizes transposon) was bred germ-cell transposition events, allowing us to generate many mutant mice. All genes 4-Mb region original donor site were mutated by SB, indicating potential this system genomic studies region.

参考文章(30)
Chikara Kokubu, Yoshihide Hayashizaki, Matthias Wahl, Misao Suzuki, Kuniya Abe, Kenji Imai, Ken Ichi Yamamura, Fabio Santagati, Tomoko Kokubu, Bettina Wilm, Isabel Rodrigo, Norio Sakai, Undulated short-tail deletion mutation in the mouse ablates Pax1 and leads to ectopic activation of neighboring Nkx2-2 in domains that normally express Pax1. Genetics. ,vol. 165, pp. 299- 307 ,(2003) , 10.1093/GENETICS/165.1.299
Vicki Rosen, Karen M. Lyons, Soyun E. Yi, Aaron Daluiski, Ron Pederson, The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. Development. ,vol. 127, pp. 621- 630 ,(2000)
Stephen R. Yant, Xiaolin Wu, Yong Huang, Brian Garrison, Shawn M. Burgess, Mark A. Kay, High-resolution genome-wide mapping of transposon integration in mammals. Molecular and Cellular Biology. ,vol. 25, pp. 2085- 2094 ,(2005) , 10.1128/MCB.25.6.2085-2094.2005
Rebecca S. Devon, David J. Porteous, Anthony J. Brookes, Splinkerettes—improved vectorettes for greater efficiency in PCR walking Nucleic Acids Research. ,vol. 23, pp. 1644- 1645 ,(1995) , 10.1093/NAR/23.9.1644
Robert-Jan Palstra, Bas Tolhuis, Erik Splinter, Rian Nijmeijer, Frank Grosveld, Wouter de Laat, The beta-globin nuclear compartment in development and erythroid differentiation. Nature Genetics. ,vol. 35, pp. 190- 194 ,(2003) , 10.1038/NG1244
Adam J. Dupuy, Sabine Fritz, David A. Largaespada, Transposition and gene disruption in the male germline of the mouse. Genesis. ,vol. 30, pp. 82- 88 ,(2001) , 10.1002/GENE.1037
Adam J. Dupuy, Keiko Akagi, David A. Largaespada, Neal G. Copeland, Nancy A. Jenkins, Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system Nature. ,vol. 436, pp. 221- 226 ,(2005) , 10.1038/NATURE03691
Marvin L Meistrich, Chad M Wayne, Carol Maclead, Manjeet Rao, Mingang A Chen, Shirley R Bruce, Miles F Wiikinson, James A MacLean, None, Rhox: a new homeobox gene cluster. Cell. ,vol. 120, pp. 369- 382 ,(2005) , 10.1016/J.CELL.2004.12.022
, The knockout mouse project Nature Genetics. ,vol. 36, pp. 921- 924 ,(2004) , 10.1038/NG0904-921
H. Kiyosawa, T. Kawashima, D. Silva, N. Petrovsky, Y. Hasegawa, K. Sakai, Y. Hayashizaki, Systematic genome-wide approach to positional candidate cloning for identification of novel human disease genes Internal Medicine Journal. ,vol. 34, pp. 79- 90 ,(2004) , 10.1111/J.1444-0903.2004.00581.X