RIKEN

Supply of services related to disease mouse models and compilation of internationally standardized data

Application of animal models is useful in drug discovery researches, and large-scale knockout mouse projects are about to begin in Europe and the United States, at present. Also, in Japan, in order to promote the drug discovery researches effectively, it is important to compile the resources concerning disease mouse models and develop technology to use the resources.

Mouse platform uses the resources archived at RIKEN BioResource Center (BRC), which is known as the core of the worldwide mouse resource centers as well as the Jackson Laboratory (the United States) and European Mouse Mutant Archive (EMMA), and supports reinforcement of the disease mouse model platform and its active application. Specifically, in addition to osteoarthritis (OA) mouse model, mouse platform offers more than 60 kinds of human disease mouse models inside and outside Riken. In addition, high throughput mouse phenotype analyses are conducted for 400 test items for 26 weeks with the comprehensive and highly standardized screening procedures established by BRC Japan Mouse Clinic, and statistical numerical data and disease phenotype data which enables us to compare directly among mouse strains is compiled. Moreover, for data such as mouse strain names, genes and mutants, protocols, and phenotype names, mouse platform offers mouse phenotype data which is useful for drug discovery development by establishment of database in accordance with the internationally standardized data framework.

To propel drug discovery researches, Riken develops 2 technology platforms of mouse phenotype analysis technology and well-developed human disease mouse models, and supports various drug discovery researches through offering the tools for drug efficacy and pharmacokinetic studies.

More than 60 kinds of human disease mouse models

In addition to 62 kinds of the human disease mouse models whose gene responsible for mutation has already been identified from the previous research results, mouse platform develops various mutant mice categorized by disease (Table 1).

Mutant Mouse Phenotype Database “PhenoSITE”

Detail information on the above mutant mice is available on the website of “PhenoSITE (Phenotype Semantic Information with Terminology of Experiments)”, a web database integrating the mouse phenotyping platform and the experimental procedures in mice of RIKEN Genomic Sciences Center (GSC) (Fig.1 ). Moreover, browsing mutant data, standard data, and analysis SOPs (standard operation procedures), and application for delivery of mutant mice are available on the website.

Click here for Mutant Mouse Phenotype Database “PhenoSITE”

Mouse phenotype analysis system which allows us to conduct screening for 400 test items for 26 weeks

Until now, RIKEN Genomic Sciences Center (GSC) has established phenotype analysis platform, made a concentrated effort to discover mutant mice, and focused on the development of the mouse models. As a result, in addition to more than 60 kinds of human disease mouse models, a number of useful mouse models have been developed successfully. In order to use the previous research results inside and outside RIKEN, mouse platform conducts comprehensive phenotype analyses of human disease mouse models and expands information of the numerical data (Fig. 2). In the comprehensive phenotype analysis of disease mouse models, screening is conducted systematically for a short period of 26 weeks at BRC Japan Mouse Clinic for about 400 test items including Modified-SHIRPA, in which behaviors and appearance are observed by visual inspection, blood picture test, urinalysis, clinical biochemical test, seizure induction test by pentylenetetrazole (PTZ), X-ray imaging, behavior oriented tests such as open field test, passive avoidance tests, and home cage activity test, blood pressure measurement, and autopsy. In addition, some tests are conducted to screen for aging-related pathology/ phenotypes in the mice bred for a long time. For the numerical data obtained from these tests, since the measurement values are not always normally distributed, but strain or sex differences are sometimes observed, Box-Cox transformation is used to approach the distorted data to the normal distribution. At the same time, statistical evaluation is conducted to set the standard ranges for each of strains and sexes, and a system is developed in order to show abnormal values clearly and compare phenotype data directly among mutant mouse strains on the same standard. Moreover, in the information expansion of phenotype numerical data of disease mouse models, the data obtained from &ldquoMouse Clinic&rdquo is archived at the Integrated Database in RIKEN Life Science field, and is linked with the individual information such as terminologies suitable for the internationally standardized data framework and mouse strain names, genes and gene mutants, detail phenotype analysis methods, evaluation of each numerical values, and phenotype names using predicate information links to define the relation with human disease data focused on the phenotypes of these disease mouse models.