Mutagenesis and Genomics Team

Efficient mutagenesis technologies and mutation detection systems are indispensable to develop biological resources. The genome-wide mutation discovery is also a key for the quality control of archived bioresources. The Mutagenesis and Genomics Team will develop a high-throughput and high-resolution mutation discovery system in particular to detect unknown newly-arisen mutations in the whole genome of higher eukaryotes. At the same time, we will develop useful mutagenesis infrastructures and technologies and indeed provide useful bioresources such as model mice for human diseases to the research community. We, for instance, used a potent mutagen, ethylnitrosourea (ENU) to induce point mutations in the mouse genome. Then the mutation discovery system allows us to detect randomly induced single-base-substitutions in any target genes. Contrary to ordinary genetics, it is called "reverse genetics" or "gene-driven mutagenesis", which provides mutant mouse lines to understand the biological function of the gene and genome. Mutant mice carrying mutations in candidate genes for human diseases are subjected to study the mechanism of the diseases. In particular, so-called "next-generation sequencing technology" is currently being developed at the astonishing pace and scale. We integrate such state-of-arts technologies to the ultra-throughput detection system of mutations and polymorphisms for the development of human disease models as well as the quality control of our bioresources. The integrated system is now enable to establish new model mice encompassing the gene-to-gene interaction(s). The feasibility to establish polygenic model mice has already been shown by the comprehensive discovery of all the coding mutations by the next-generation sequencers with the whole mouse coding-exon enrichment system.

Research Subjects

• Development of ENU-based gene-driven mutagenesis and modeling human diseases in the mouse.
• Development of the mutation discovery system for newly-arisen mutations and polymorphisms with next-generation techonologies.
• Development of resources for the functional genomics including human and mouse gene-to-gene interactions.
• Maintenance of bioresource based on mutations, recombinations and rearrangements of the genome.
• Development of model systems for the highly conserved noncoding genomic sequences in the genome.

Publications

1. Gondo Y.:
   "Mouse models for human diseases by forward and reverse genetics."
   Animal Models for the Study of Human Disease. Ed. By Conn, P.M., 2013, in press.
2. Shoji H, Toyama K, Takamiya Y, Wakana S, Gondo Y, Miyakawa T.:
   "Comprehensive behavioral analysis of ENU-induced Disc1-Q31L and -L100P mutant mice."
   BMC Res Notes 5: 108. doi: 10.1186/1756-0500-5-108, 2012.
3. Gondo Y, Murata T, Makino S, Fukumura R, Ishitsuka Y.:
   "Mouse mutagenesis and disease models for neuropsychiatric disorders."
   Current Topics in Behavioral Neurosciences 7: 1-35, 2011.
4. Lazar N, Singh S, Paton T, Clapcote S, Gondo Y, Fukumura R, Roder J, Cain D.:
   "Missense mutation of the reticulon-4 receptor alters spatial memory and social interaction in mice."
   Behavioural Brain Research 224(1): 73-79, 2011.
5. Janes DE, Chapus C, Gondo Y, Clayton DF, Sinha S, Blatti CA, Organ CL, Fujita MK, Balakrishnan CN, Edwards SV.:
   "Reptiles and mammals have differentially retained long conserved non-coding sequences from the amniote ancestor."
   Genome Biol Evol 3: 102-113, 2011.
6. Gondo Y, Fukumura R, Murata T, Makino S.:
   "ENU-based gene-driven mutagenesis in the mouse: a next-generation gene-targeting system."
   Exp Anim. 59(5): 537-548, 2010.
7. Gondo Y.:
   "Now and future of mouse mutagenesis for human disease models."
   J Genet Genomics 37(9): 559-572, 2010.
8. Gondo Y, Fukumura R.:
   "ENU-induced mutant mice for a next-generation gene-targeting system."
   Progress in Brain Research 179: 29-34, 2009.
9. Viviane L, Fukumura R, Rastogi A, Fick LJ, Wang W, Boutros PC, Kennedy JL, Semeralul MO, Lee FH, Baker GB, Belsham DD, Barger SW, Gondo Y, Wong AHC, Roder JC.:
   "Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model."
   Human Molecular Genetics 18(17): 3227-3243, 2009.
10. Gondo Y.:
    "Trends in large-scale mouse mutagenesis: from genetics to functional genomics."
    Nature Reviews Genetics 9: 803-810, 2008.