International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 6 - GENE-DRIVEN MUTAGENESIS FOR MOUSE MUTANTS WITH NEUROLOGICAL GENES

Sezutsu H
Population and Quantitative Genomics Team, RIKEN Genomic Sciences Center

Co-Authors: 2) Wada Y, 1) Takahasi KR, 1) Sakuraba Y, 1) Kaneko S, 1)Fujimoto N, 1) Tsuchihashi K, 1) Matsumoto R, 2) Wakana S, 2) Noda T, 2) Shiroishi T, 1) Gondo Y
Institutions: 1) Population and Quantitative Genomics Team, RIKEN Genomic Sciences Center, 2) Mouse Functional Genomics Research Group, RIKEN Genomic Sciences Center

We have developed a system for gene-driven ENU mutagenesis to produce recessive mutants efficiently. In our mouse mutagenesis project, all the G1 sperms have been cryopreserved in liquid nitrogen to retain any G1 male strains for late-onset phenotype screening. The genomic DNAs from all the G1 males are also extracted from the testes. DNAs were already extracted from more than 6,000 individuals. From each G1's DNA, any target genes are amplified by PCR and ENU-induced mutations are then identified by direct sequencing or TGCE (Temperature Gradient Capillary Electrophoresis). The point mutations are then examined in vivo by retrieving the sperm from the liquid nitrogen or natural mating, and producing the viable G3 mice. To elucidate a molecular basis of behavior, emotion and neurodegenerative disease, and to understand their complex traits in individuals, we have been screening for mutants with emotional/mental, nervous system, and neurodegenerative diseases related genes. For example, dopamine receptor 4, arginine vasopressin receptor 1A and so on have been screened as target genes. G3 mice are subjected to standard phenotype screening and tested for behavioral phenotypes in detail. We will discuss about the progress of the gene-driven mutagenesis for these genes.


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