The information center is the hub and glue of the National BioResource Project (NBRP). The center provides the NBRP portal site and has also contributed to the development of databases for diverse types of bioresources. The program covers information on experimental living organisms as the core of NBRP, and on specimens of biodiversity related to the activities of the Japan node of the Global Biodiversity Information Facility (GBIF). The framework of the former and the information facility of the latter are introduced.

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Mice are one of the most important model organisms for studying biological phenomena and diseases processes in life sciences. The biomedical research community has succeeded in launching large scale strategic knockout mouse projects around the world. RIKEN BRC, a comprehensive government funded biological resource center was established in 2001. RIKEN BRC has been acting as the core facility for the mouse resources of the National BioResource Project (NBRP) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan since 2002. RIKEN BRC is a founding member of the Federation of International Mouse Resources (FIMRe) together with the Jackson Laboratory, the European Mouse Mutant Archive, and other centers, and has participated in the International Mouse Strain Resource (IMSR) to distribute mouse strains worldwide. With the support of the scientific community, RIKEN BRC has collected over 3,800 strains including inbred, transgenic, knockout, wild-derived, and ENU-induced mutant strains. Excellent mouse models for human diseases and gene functions from academic organizations and private companies are distributed through RIKEN BRC. To meet research and social needs, our mice will be rederived to a specific pathogen-free state, strictly monitored for their health, and accurately tested for their genetic modifications and backgrounds. Users can easily access our mouse resources through the internet and obtain the mouse strains for a minimal fee. Cryopreservation of embryos and sperm is used for efficient preservation of the increasing number of mouse resources. RIKEN BRC collaborates with FIMRe members to support Japanese scientists in the use of valuable mouse resources from around the world.

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Cellular slime molds are eukaryotic microorganisms in the soil. They feed on bacteria as solitary amoebae but conditionally construct multicellular forms in which cell differentiation takes place. Therefore, they are attractive for the study of fundamental biological phenomena such as phagocytosis, cell division, chemotactic movements, intercellular communication, cell differentiation, and morphogenesis. The most widely used species, Dictyostelium discoideum, is highly amenable to experimental manipulation and can be used with most recent molecular biological techniques. Its genome and cDNA analyses have been completed and well-annotated data are publicly available. A larger number of orthologues of human disease-related genes were found in D. discoideum than in yeast. Moreover, some pathogenic bacteria infect Dictyostelium amoebae. Thus, this microorganism can also offer a good experimental system for biomedical research. The resources of cellular slime molds, standard strains, mutants, and genes are maintained and distributed upon request by the core center of the National BioResource Project (NBRP-nenkin) to support Dictyostelium community users as well as new users interested in new platforms for research and/or phylogenic consideration.

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The genotype-phenotype relationship was examined experimentally for the Pax6^Sey-4H mutant, which carries deletion of its chromosome 2 middle region hemizygously. The genotyping has indicated that this deleted segment is between 102.6 and 109.2 Mb from the centromere. The glucose-6-phosphatase gene followed by the glucagon and carboxyl ester lipase genes were mapped adjacent to the deleted region. Phenotyping indicates that the Pax6^Sey-4H mutant is more susceptible to diabetes. The glucose tolerance test showed that the mutants were less capable of reducing their level of blood glucose to the standard level than the normal sibs. The insulin-loading test revealed their inability to elevate their blood glucose levels up to normal levels. The time it took for the onset of diabetes induced by streptozotocin was shorter in the mutants than in normal sibs. Both the haploinsufficiency of the genes in the hemizygous segment of chromosome 2 and the quantitative imbalance of the whole genome could contribute the development of this phenotype in the mutant.

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Atherosclerosis is thought to be associated with endoplasmic reticulum (ER) dysfunction and the accumulation of unfolded proteins. In this study, we examined the relationship between atherosclerosis and ER stress and the effect of sodium 4-phenylbutyrate (4-PBA), a kind of chemical chaperone, on atherosclerosis in streptozotocin-induced diabetic APA hamsters. Male, 8-week-old, APA hamsters were injected with streptozotocin (30 mg/kg body weight) to induce diabetes mellitus, and ER stress was evaluated immunohistochemically or by semi-quantitative RT-PCR analysis using ER stress markers such as calreticulin and GPR78. Control hamsters were injected with citrate buffer and were similarly analyzed. In the aorta of control animals, a weak ER stress was detected, and 4-PBA treatment decreased the calreticulin- and GRP78-positive areas and also reduced the mRNA levels of calreticulin and GRP78. On the other hand, strong ER stress was detected at the lesser curvature of the aortic arch of streptozotocin-induced diabetic APA hamsters. However, 4-PBA treatment failed to lessen the ER stress in the aorta and had no effect on improvement of the atherosclerotic lesions. These results may provide an explanation for the complex etiology of atherosclerosis accompanied by diabetes mellitus and various other clinical phenotypes of atherosclerosis.

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Most laboratory mice belong to a species of house mouse, Mus musculus. So far, at least three subspecies groups have been recognized; domesticus subspecies group (DOM) distributed in western Europe, musculus subspecies group (MUS) distributed in eastern Europe and northeast Asia, and castaneus subspecies group (CAS) found in southwest and southeast Asia including southern China. These subspecies are estimated to have branched off roughly one million years ago. Genetic comparison between subspecies' groups and common inbred strains (CIS) have revealed that the genetic background of CIS is derived mainly from DOM. This shows the importance of non-DOM wild mice as valuable genetic resources. We started to establish our unique strain, MSM/Ms, from MUS in Japan in 1978. In the beginning, we kept wild mice trapped in Mishima in large plastic buckets. In 1979, breeding by sister-brother mating started. The MSM/Ms inbred strain was established in 1986 and 21 years later it reached F₁₀₀. During breeding, no significant fluctuations in litter size and sex ratios have been observed. Extensive genetic analyses of chromosome C-banding pattern, biochemical markers and microsatellite DNA (MIT) markers of this strain have demonstrated the characteristics of MUS. A phylogenetic tree constructed from MIT markers has confirmed the MUS nature of MSM strain. Taken together with its genetic remoteness from CIS, MSM appears to maintain many valuable alleles for investigation of biological functions and diseases. Some of these alleles have avoided selection during breeding as either fancy mice or laboratory mice. The MSM-specific genetic traits discovered to date are discussed.

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The RNA polymerase gene of murine norovirus (MNV) was isolated from feces and organ samples by the reverse transcription (RT)-polymerase chain reaction (PCR). For experimental infection, homogenate of cecum obtained from an MNV-infected mouse was gavaged to 3 C.B-17-Prkdc^scid (scid) mice and 3 ICR mice at 6 weeks of age. Sixty days after oral inoculation, MNV was isolated from the cecum (3/3 scid and 3/3 ICR), feces (3/3 scid and 3/3 ICR), duodenum (1/3 scid and 3/3 ICR), liver (1/3 scid and 1/3 ICR), and spleen (3/3 ICR) samples, but MNV was not detected in the brain, heart, kidney, lung, salivary gland, ovary, thymus, or uterus samples of any of the orally inoculated mice. Feces of males cohabiting with MNV infected dams were positive for viral RNA after 18 days of cohabitation, but 8 fetuses (embryonic day 18.0) derived from the dams were negative for the virus. The results suggest that the cecum and feces are the most suitable sample types for the detection of MNV in infected animals and that caesarean section is efficient for the elimination of the virus. In terms of spontaneous infection, the RNA polymerase gene of MNV was isolated from 33/245 (13.1%) cecum samples derived from 15/59 (25.4%) facilities, and the sequence analysis revealed that at least 5 types of the virus were prevalent. This is the first report on MNV infection in mouse colonies in Japan.

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The C57BL/6 mouse is the most well-known inbred mouse strain, and has been widely used as a genetic background for congenic and mutant mice. A number of C57BL/6 substrains have been derived from the C57BL/6 founder line and are reported to differ in several phenotypes. There are several major sources of C57BL/6 substrains for the biomedical research community. The importance of their genetic and phenotypic differences among substrains, however, has not yet been well recognized by biomedical researchers. Here, we report the result of screening of the functional deletion of the nicotinamide nucleotide transhydrogenase (Nnt) gene and 1,446 SNPs genotyping among seven C57BL/6 substrains from different sources, such as C57BL/6J, C57BL/6JJcl, C57BL/6JJmsSlc, C57BL/6NJcl, C57BL/6NCrlCrlj, C57BL/6NTac, and C57BL/6CrSlc. The deletion of exon 7-11 in the Nnt gene that was previously reported in C57BL/6J was also observed in other C57BL/6J substrains, indicating that this functional deletion probably occurred at an early stage in the establishment of C57BL/6J substrains. The genotyping of SNP loci clearly demonstrate genetic differences between C57BL/6J and C57BL/6N substrains at 11 loci. Besides, we found another SNP differing between C57BL/6J and other C57BL/6J substrains available from commercial breeders. No genetic difference was detected among C57BL/6N substrains. The C57BL/6CrSlc mouse, originally derived from the National Cancer Institute of the NIH was found to be the same as the C57BL/6N substrains by the SNP pattern. These data will be useful for accurate genetic monitoring of genetically engineered mice with the C57BL/6 background.

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The present study investigated whether pre-stimulation with intraperitoneal (i.p.) needling protects against development of diabetes in alloxan-treated transgenic (Tg) mice overexpressing the human Cu/Zn superoxide dismutase gene or non-Tg littermates of the FVB/N strain. Twenty minutes before the alloxan treatment (60mg/kg) the mice were injected intraperitoneally with 0.05ml saline while control mice received only the alloxan treatment. Hyperglycemic responses of the saline-injected mice to alloxan were significantly suppressed in the Tg mice (P<0.05). A similar reduction of response was also observed in non-Tg littermates, but the effect was less than that in the Tg mice. This protective effect on the diabetogenic action of alloxan was also demonstrated by an analysis of the number of days positive for urinary glucose, and by immunohistochemical analysis of pancreatic insulin-positive cells. A similar suppressive effect on the hyperglycemic response of alloxan was observed in the mice stimulated by i.p. needling alone. However, suppression of the hyperglycemic response was not observed in ICR mice receiving an i.p. injection. These results suggest that the diabetogenic action of alloxan can be suppressed by i.p. needling-mediated stimulation in mice that have a genetic background of the FVB/N strain. Since a slight protective effects of alloxan-induced diabetes was also observed in the Tg mice compared to FVB/N mice treated with only alloxan, this phenomenon could be more clearly seen in the Tg mice than in non-Tg littermates with an FVB/N background.

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Diversity in T cell recognition of antigens is determined by diverse usage of T cell receptor (TCR) repertoire. TCR repertoire analysis provides fundamental information for understanding T cell immune responses in the pathogenesis of various diseases. In the present study, we examined the TCR repertoire in various tissues in normal BALB/c mice. The TCR α chain variable region repertoires were consistent among the spleen, lymph nodes, and the thymus. The TCR β chain variable region (TCRBV) repertoires were consistent between the spleen and lymph nodes, but different in the thymus. The TCR repertoires also differed in the lungs and the intestinal tract. The TCR repertoires were consistent between male and female mice, except for TCRBV15-1. TCR repertoire was almost similar in 3- and 7-week-old mice, except for TCRBV1-1, 8-3, and 14-1. The present findings suggest that the TCR repertoire of mice varies according to tissue type, sex and age. Additional analysis of the TCR repertoire, i.e., the effect of hydrocortisone (HC), was carried out. After the HC treatment, although the thymic T cells decreased to one-tenth, only a small fraction of CD4⁺CD8⁺ T cells survived the treatment. Furthermore, the percentages of thymic T cells bearing TCRBV3-1, 5-1, 5-2, and 16-1 substantially decreased, but the percentage of cells bearing TCRBV12-1 did not decrease. The present findings suggest that the HC susceptibility of immature thymic T cells is different between TCR families.

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Histocompatibility was assessed in the RIR-Y8/NU, BL-E, YL, and WL-G chicken closed colonies by hemagglutination test using anti-red blood cell (RBC) antibodies (HT), skin transplantation test (STT), and formation of isohemagglutinins (FIHs) during STT. The YL individuals all showed the survival of skingrafts for more than 17 days with no FIHs in STT and no RBC antigenic variations in HT, indicating a histocompatible nature together with high homogeneity at serological loci. The BL-E as well as WL-G closed colonies were also found to be histocompatible in the STT with no FIHs, although the HT showed heterogeneities at serological locus/loci other than the B and C blood group loci which have significant effects on histocompatibility or FIHs in chicken. In the RIR-Y8/NU closed colonies, one individual in 6 reciprocal combinations of the STT showed early skingraft rejection with positive FIHs caused by different B locus alleles, and the HT suggested relatively high heterogeneities at the other serological loci too. The closed colonies of YL, BL-E, and WL-G will be useful avian materials for transplantation or related experiments, but RIR-Y8/NU needs further pedigree selection for serological homogeneity.

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Although the effect of taurine on the heart and liver is well studied, there has been no direct observation concerning the effect of taurine on spatial learning and memory at the behavior level. In this study, we tested the effect of subacute taurine supplementation with evaluation by the Morris water maze method. Although swim distance to find the platform of taurine-supplemented rats was significantly longer than that of control rats due to increase of swimming velocity, escape latency and the efficacy of learning and memory was comparable in both groups. These results suggest that taurine supplemented orally does not affect the learning and memory function.

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Recent studies have focused on the association between primary osteoarthritis and dyslipidemia. STR/Ort mice have unique characteristics including osteoarthritis and hyperlipidemia, and may be a useful model for investigating the effect of dyslipidemia on the underlying mechanism of primary osteoarthritis. However, little is known about the hyperlipidemic properties of STR/Ort mice. In this study we investigated hyperlipidemia and lipotoxicity in STR/Ort mice. STR/Ort mice have human hyperlipidemic patient-like symptoms such as hypercholesteremia, hypertriglyceridemia, hyperinsulinemia, insulin resistance, dysregulation of NEFA, and low serum adiponectin. Excess triglyceride accumulation in the liver of STR/Ort mice was not observed even when they exhibited hyperinsulinemia. This information may be useful for researchers investigating lipid metabolism and primary osteoarthritis using STR/Ort mice.

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We developed a new cage lid made of stainless steel wire mesh and having a screen barrier for partitioning a small laboratory animal cage into compartments. To evaluate the effectiveness of the lid, we tested the transmissibility of Cilia-Associated Respiratory (CAR) bacillus from infected mice to uninfected sentinel mice, which were kept in separate compartments using this lid. Infection from the infected mice to the uninfected mice was confirmed by microbiological, serological, pathological, and molecular diagnostic examinations, as previously observed in an intra-cage contact route. The cage lid that we developed is very useful when uninfected mice are used in quarantine and contagion experiments to prevent fighting among the mice.

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Genetic bases of glomerulonephritis, a major cause of kidney dysfunction in humans and one of the most characteristic complications of autoimmune disorders such as Goodpasture syndrome, are complex. The Wistar-Kyoto (WKY) rat strain is well characterized for its susceptibility to autoantibodies against glomerular basement membrane (GBM), however the molecular mechanisms underlining the phenotype are largely unknown. Here we performed a whole genome scan using a backcross (BC) F₁ (WKY × DA) × WKY population, for which the DA rat is a nonsusceptible control strain. We found two significant QTLs on chromosomes 1 and 12, which were involved in elevated levels of proteinuria and kidney weight index, respectively. The relevance of these QTLs with the genetic factors involved in autoimmunity and renal disease is discussed.

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