International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


ORAL PRESENTATION

MONDAY 10 NOVEMBER
10:00 – 10:15 HRS

FUNCTIONAL ANALYSIS OF THE MOUSE GENOME BY GENE TRAP MUTAGENESIS

Floss T
GSF Institute of Developmental Genetics

Co-Authors: (1) Seisenberger C, (2) Ruiz P, (3) van Sloun P, (3) Schnütgen F, (4) Füchtbauer EM, (5) Franz Vauti, (5) Arnold HH, (1) Hansen J, (3) von Melchner H, (1) Wurst W.
Institutions: (1) GSF Institute of Developmental Genetics, (2) Max-Planck Institute Berlin, (3) University of Frankfurt, (4) University of Arhuis, (5) Technical University of Braunschweig

Gene trap mutagenesis in mouse embryonic stem (ES) cells is a complementary approach to the functional annotation of the mouse genome. In concert with chemical (ENU) mutagenesis, this approach is accelerating the analysis of gene function in the context of the entireorganism and thus furthers our understanding of human disease. We have established a Research Consortium (German Gene trap Consortium, GGTC) to carry out large scale gene trap mutagenesis in ES cells. Its goal is to contribute to the saturation mutagenesis of the mouse genome and to generate a mouse model for each gene in cooperation with the International Mouse Mutant Consortium (IMMC). Towards this goal, the GGTC has generated 20,000 mutant ES cell lines by utilizing four different vectors and it has identified the gene trap integration sites in 11,626 clones. Of the generated gene trap sequence tags (GTSTs), 7,453 informative sequences were obtained of which 5,119 corresponded to known genes, 811 to ESTs and 1,604 to putative novel genes. More than a hundred mouse lines have been generated within the GGTC alone. After analysing 30 mutant lines in the F2 generation, the mutagenicity of different vector types was compared in terms of “embryonic lethality”, “obvious” and “not obvious” phenotype. The complete abscence of wildtype protein or mRNA was demonstrated for a number of mutants. In summary, 59% of the mutants exhibit either lethality or obvious phenotypes. This frequency is comparable to results that were obtained by conventional gene targeting experiments.


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