To date, various human diseases have been elucidated at the gene level, and genetic analyses are performed in clinical practice. Meanwhile, research aimed at identifying genes responsible for remaining human diseases is being performed by using accumulated human DNA sequence data from patients. Even diseases with similar symptoms can be distinguished by identification of genes responsible for the diseases. Analysis of mutations in the human genome can inform us about the risk that an individual will be predisposed to a certain disease. Our team is also producing mouse models of human disease by introducing the relevant genetic mutations into the mouse genome. The availability of excellent mouse models of human disease, in conjunction with our genome engineering technology, will provide a greater understanding of human disease. We would be pleased if the information and knowledge resulting from our research were able to promote development of therapeutic medicines and diagnostic methods.
  As the pathogenic mechanism of various types  of human disease is elucidated, more complicated and precise genome engineering  technologies are needed to produce mouse models of complex human diseases. We  have developed two novel site-specific recombination systems that can eliminate  or invert any DNA region on the genome; these technologies have been patented.  We have successfully used these novel site-specific recombination systems to  modify the mouse genome. We are developing an improved human artificial  chromosome (HAC) technology by adapting these site-specific recombination  systems. As described above, we are focusing on developing genome engineering  technologies. 
   As a collaboration with an outside research  institution, we are proceeding with a project called “Establishment of  pipe-line system for systematical production of conditional knockout mice to  identify genes responsible for human common disease.”  Via this collaboration, we hope to make a  specific contribution to solving human health problems.
  We are attempting to generate mouse models of  human disease by introducing the single-nucleotide polymorphisms (SNPs) related  to human disease (i.e., SNPs identified in current or future patients) into the  mouse genome. Such research will help to determine whether these SNPs are  responsible for the disease. From the results of these studies, we will obtain  useful basic information and knowledge regarding human disease, and this  knowledge will in turn contribute to the development of novel therapeutic  approaches. By improving an existing high-throughput DNA sequencing system  using clinical samples from patients or healthy individuals, we are aiming at developing  a system capable of generating diagnostic DNA data that will be useful in  clinical practice in the future.
   We will provide our technical know-how,  accumulated during the production of disease models in mice, to research  institutes and private companies inside and outside Chiba prefecture because we  hope to aggressively promote cooperation with the industrial sector.
| Manabu Nakayama | team leader | nmanabu at kazusa.or.jp |