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

被引：90

作者：

Keng, VW

Yae, K

Hayakawa, T

Mizuno, S

Uno, Y

Yusa, K

Kokubu, C

Kinoshita, T

Akagi, K

Jenkins, NA

Copeland, NG

Horie, K

Takeda, J

机构：

[1] Osaka Univ, Ctr Adv Sci & Innovat, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Dept Social & Environm Med, Grad Sch Med, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan

[4] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA

来源：

NATURE METHODS | 2005年 / 2卷 / 10期

关键词：

D O I：

10.1038/NMETH795

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent consolidation of the whole-genome sequence with genome-wide transcriptome profiting revealed the existence of functional units within the genome in specific chromosomal regions, as seen in the coordinated expression of gene clusters and colocatization 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.

引用

页码：763 / 769

页数：7

共 30 条

[1] The knockout mouse project [J].

Austin, CP ;

Battey, JF ;

Bradley, A ;

Bucan, M ;

Capecchi, M ;

Collins, FS ;

Dove, WF ;

Duyk, G ;

Dymecki, S ;

Eppig, JT ;

Grieder, FB ;

Heintz, N ;

Hicks, G ;

Insel, TR ;

Joyner, A ;

Koller, BH ;

Lloyd, KCK ;

Magnuson, T ;

Moore, MW ;

Nagy, A ;

Pollock, JD ;

Roses, AD ;

Sands, AT ;

Seed, B ;

Skarnes, WC ;

Snoddy, J ;

Soriano, P ;

Stewart, DJ ;

Stewart, F ;

Stillman, B ;

Varmus, H ;

Varticovski, L ;

Verma, IM ;

Vogt, TF ;

von Melchner, H ;

Witkowski, J ;

Woychik, RP ;

Wurst, W ;

Yancopoulos, GD ;

Young, SG ;

Zambrowicz, B .

NATURE GENETICS, 2004, 36 (09) :921-924

[2] The European dimension for the mouse genome mutagenesis program [J].

Auwerx, J ;

Avner, P ;

Baldock, R ;

Ballabio, A ;

Balling, R ;

Barbacid, M ;

Berns, A ;

Bradley, A ;

Brown, S ;

Carmeliet, P ;

Chambon, P ;

Cox, R ;

Davidson, D ;

Davies, K ;

Duboule, D ;

Forejt, J ;

Granucci, F ;

Hastie, N ;

de Angelis, MH ;

Jackson, I ;

Kioussis, D ;

Kollias, G ;

Lathrop, M ;

Lendahl, U ;

Malumbres, M ;

von Melchner, H ;

Müller, W ;

Partanen, J ;

Ricciardi-Castagnoli, P ;

Rigby, P ;

Rosen, B ;

Rosenthal, N ;

Skarnes, B ;

Stewart, AF ;

Thornton, J ;

Tocchini-Valentini, G ;

Wagner, E ;

Wahli, W ;

Wurst, W .

NATURE GENETICS, 2004, 36 (09) :925-927

[3] Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation [J].

Ayyanathan, K ;

Lechner, MS ;

Bell, P ;

Maul, GG ;

Schultz, DC ;

Yamada, Y ;

Tanaka, K ;

Torigoe, K ;

Rauscher, FJ .

GENES & DEVELOPMENT, 2003, 17 (15) :1855-1869

[4] Insertional mutagenesis in mice: New perspectives and tools [J].

Carlson, CM ;

Largaespada, DA .

NATURE REVIEWS GENETICS, 2005, 6 (07) :568-580

[5]

Carlson CM, 2003, GENETICS, V165, P243

[6] The human transcriptome map:: Clustering of highly expressed genes in chromosomal domains [J].

Caron, H ;

van Schaik, B ;

van der Mee, M ;

Baas, F ;

Riggins, G ;

van Sluis, P ;

Hermus, MC ;

van Asperen, R ;

Boon, K ;

Voûte, PA ;

Heisterkamp, S ;

van Kampen, A ;

Versteeg, R .

SCIENCE, 2001, 291 (5507) :1289-+

[7] Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse [J].

Collier, LS ;

Carlson, CM ;

Ravimohan, S ;

Dupuy, AJ ;

Largaespada, DA .

NATURE, 2005, 436 (7048) :272-276

[8] SPLINKERETTES IMPROVED VECTORETTES FOR GREATER EFFICIENCY IN PCR WALKING [J].

DEVON, RS ;

PORTEOUS, DJ ;

BROOKES, AJ .

NUCLEIC ACIDS RESEARCH, 1995, 23 (09) :1644-1645

[9] Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system [J].

Dupuy, AJ ;

Akagi, K ;

Largaespada, DA ;

Copeland, NG ;

Jenkins, NA .

NATURE, 2005, 436 (7048) :221-226

[10] Transposition and gene disruption in the male germline of the mouse [J].

Dupuy, AJ ;

Fritz, S ;

Largaespada, DA .

GENESIS, 2001, 30 (02) :82-88

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