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Mammalian Genetics Laboratory • Shiroishi Group

Integrative genetics of mouse complex traits
Professor                 SHIROISHI, Toshihiko       tshirois 
Assistant Professor      TAMURA, Masaru      
matamura 
Assistant Professor       TAKADA, Toyoyuki        ttakada 
Homepage URL :  http://www.nig.ac.jp/labs/MamMalg/home-j.html
In order to understand genetic basis underlying complex traits, such as morphology and energy metabolism, we are conducting genetic analyses based upon both of “Forward Genetics” with existing mutants and“Reverse Genetics” with genetically engineered mice. In parallel, we are also compiling comprehensive information of the genome diversity of inbred mouse strains, and developing new inter-subspecific consomic strains, in which every chromosome of a classical inbred strain C57BL/6J is replaced by the counterpart of a wild mouse-derived MSM/Ms strain. These bio-resources are fully used for genetic dissection of the complex traits. Current ongoing research projects are as follows:

1. Genetic studies on developmental regulations
 • Chromosomal dynamics at the Sonic hedgehog (Shh) locus
 • Evolution of cis-regulation systems of developmental genes
 • Genetic regulation of craniofacial development and osteopenesis
2. Establishment of experimental systems for genetic dissection of complex traits, based on the genome diversity of mouse strains.
 • Collection and compilation of information of genome diversity and phenotypes of mouse strains
 • Genetic mechanism of reproductive isolation in mice
 • Genetic regulation of energy metabolism
 • Genetic basis of mouse morphological diversity

Reproductive isolation of mice due to stage-specific spermatogenesis defects. A) The stages at which spermatogenic disruptions occur in different cases of hybrid male sterility. Downward arrows indicate the spermatogenic disruptions that occur preferentially at premeiotic stage, zygotene-pachytene stage of meiosis I, and metaphase of meiosis I. Cell-cycle checkpoints are supposed to exist at these stages. B) Premeiotic cell-cycle arrest of male germ cells in the chromosome substitution strain, B6-ChrXMSM. Red indicates nuclei of meiotic spermatocytes and blue indicates all nuclei. Graph shows that number of meiotic spermatocytes in B6-ChrXMSM males is less than 10% of control males.

Oka, A., Mita, A., Takada, Y., Koseki, H., and Shiroishi, T. (2010). Reproductive isolation in hybrid mice due to spermatogenesis defects at three meiotic stages. Genetics 186, 339-51.

Sagai, T., Amano, T., Tamura, M., Mizushina, Y., Sumiyama K. and Shiroishi, T. (2009). A cluster of three long-range enhancers directs regional Shh expression in the epithelial linings. Development 136, 1665-1674.

Amano, T., Sagai T., Tanabe, H., Mizushina, Y., Nakazawa, H., and Shiroishi, T. (2009). Chromosomal dynamics at the Shh locus: limb budspecific differential regulation of competence and active transcription. Dev. Cell 16 , 47-57.

Takada, T., Mita, A., Maeno, A., Sakai, T., Shitara, H., Kikkawa, Y., Moriwaki, K., Yonekawa, H., and Shiroishi, T. (2008). Mouse intersubspecific consomic strains for genetic dissection of quantitative complex traits. Genome Res. 18, 500-598.

Tamura, M., Tanaka, S., Fujii, T., Aoki, A., Komiyama, H., Ezawa, K., Sumiyama, K., Sagai, T., and Shiroishi, T. (2007). Members of a novel gene family, Gsdm, are expressed exclusively in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner. Genomics 89, 618-629.

Oka, A., Aoto, T., Totsuka, Y., Takahashi, R., Ueda, M., Mita, A., Sakurai-Yamatani, N.,  Yamamoto, H., Kuriki, S., Takagi, N., Moriwaki, K., and Shiroishi, T. (2007). Disruption of Genetic Interaction Between Two Autosomal Regions and the X Chromosome Causes Reproductive Isolation Between Mouse Strains Derived From Different Subspecies. Genetics 175, 185-197.

Professor
SHIROISHI, Toshihiko
tshirois 
Assistant Professor
TAMURA, Masaru

matamura 
Assistant Professor
TAKADA, Toyoyuki

ttakada