文献一覧: Takahashi Satoru (著者)

Heparan sulfate endosulfatases Sulf1 and Sulf2 hydrolyze 6-O-sulfate in heparan sulfate, thereby regulating cellular signaling. Previous studies have revealed that Sulfs act predominantly on UA2S-GlcNS6S disaccharides and weakly on UA-GlcNS6S disaccharides. However, the specificity of Sulfs and their role in sulfation patterning of heparan sulfate in vivo remained unknown. Here, we performed disaccharide analysis of heparan sulfate in Sulf1 and Sulf2 knock-out mice. Significant increases in ΔUA2S-GlcNS6S were observed in the brain, small intestine, lung, spleen, testis, and skeletal muscle of adult Sulf1−/− mice and in the brain, liver, kidney, spleen, and testis of adult Sulf2−/− mice. In addition, increases in ΔUA-GlcNS6S were seen in the Sulf1−/− lung and small intestine. In contrast, the disaccharide compositions of chondroitin sulfate were not primarily altered, indicating specificity of Sulfs for heparan sulfate. For Sulf1, but not for Sulf2, mRNA expression levels in eight organs of wild-type mice were highly correlated with increases in ΔUA2S-GlcNS6S in the corresponding organs of knock-out mice. Moreover, overall changes in heparan sulfate compositions were greater in Sulf1−/− mice than in Sulf2−/− mice despite lower levels of Sulf1 mRNA expression, suggesting predominant roles of Sulf1 in heparan sulfate desulfation and distinct regulation of Sulf activities in vivo. Sulf1 and Sulf2 mRNAs were differentially expressed in restricted types of cells in organs, and consequently, the sulfation patterns of heparan sulfate were locally and distinctly altered in Sulf1 and Sulf2 knock-out mice. These findings indicate that Sulf1 and Sulf2 differentially contribute to the generation of organ-specific sulfation patterns of heparan sulfate.

2013-01-17 08:30:24
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1 0 0 0 OA Noninvasive Monitoring of β-Cell Mass and Fetal β-Cell Genesis in Mice Using Bioluminescence Imaging

著者: Sekiguchi Yukari Owada Junya Oishi Hisashi Katsumata Tokio Ikeda Kaori Kudo Takashi Takahashi Satoru
出版者: Japanese Association for Laboratory Animal Science
雑誌: Experimental animals (ISSN:13411357)
巻号頁・発行日: vol.61, no.4, pp.445-451, 2012
被引用文献数: 9 4

Bioluminescence imaging (BLI) has been applied in gene therapy and research to screen for transgene expression, progression of infection, tumor growth and metastasis, and transplantation. It enables real-time and relatively noninvasive localization and serial quantification of biological processes in experimental animals. In diabetes research, BLI has been employed for the quantification of β-cell mass, monitoring of islet graft survival after transplantation, and detection of reporter gene expression. Here, we explore the use of BLI in a transgenic mouse expressing luciferase under the control of the mouse insulin 1 promoter (MIP-Luc-VU). A previous report on MIP-Luc-VU mice showed luminescence intensities emitted from the islets correlated well with the number of islets in vitro and in vivo. In this study, we showed MIP-Luc-VU mice fed a high fat diet for 8 weeks gave rise to a greater bioluminescent signal than mice fed a regular diet for the same period of time. Conversely, there was a strong reduction in the signal observed in diabetic Mafa-deficient/Mafk-transgenic mutant mice and streptozotocin-treated mice, reflecting the loss of β-cells. Furthermore, we were able to monitor fetal β-cell genesis in MIP-Luc-VU mice during the late gestational stage in a noninvasive and repetitive manner. In summary, we show that bioluminescence imaging of mice expressing a β-cell specific reporter allows detection of changes in β-cell mass and visualization of fetal β-cell neogenesis in uteri.

2012-12-20 08:30:12
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