Updated on 2024/07/13

写真a

 
ODA Kanako
 
Organization
Brain Research Institute Center for Bioresources Assistant Professor
Title
Assistant Professor
External link

Degree

  • 博士(医学) ( 2014.3   新潟大学 )

Research Areas

  • Life Science / Developmental biology

Research History (researchmap)

  • Niigata University   Brain Research Institute Center for Bioresources Bioresource Science Branch Department of Comparative and Experimental Medicine

    2009.4

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  • 三菱化学生命科学研究所

    2005.4 - 2009.3

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Research History

  • Niigata University   Brain Research Institute Center for Bioresources   Assistant Professor

    2017.4

  • Niigata University   Brain Research Institute Center for Bioresources   Specially Appointed Assistant Professor

    2013.4 - 2017.3

Professional Memberships

 

Papers

  • Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons Reviewed

    Nanaho Fukuda, Tomoyuki Fukuda, Piergiorgio Percipalle, Kanako Oda, Nobuyuki Takei, Kevin Czaplinski, Kazushige Touhara, Yoshihiro Yoshihara, Toshikuni Sasaoka

    Cell Reports   42 ( 5 )   112398 - 112398   2023.5

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.celrep.2023.112398

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  • Importance of the Q/N-rich segment for protein stability of endogenous mouse TDP-43. Reviewed International journal

    Toshiya Sato, Kanako Oda, Seiko Sakai, Rika Kato, Saori Yamamori, Makoto Itakura, Yoshio Kodera, Masatoyo Nishizawa, Toshikuni Sasaoka, Osamu Onodera, Minesuke Yokoyama

    Scientific reports   12 ( 1 )   14923 - 14923   2022.9

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    TAR DNA-binding protein 43 kDa (TDP-43), a nuclear protein, plays an important role in the molecular pathogenesis of amyotrophic lateral sclerosis (ALS). The long-disordered C-terminal region (CTR) of TDP-43 is known to be aggregation-prone and a hotspot for ALS mutations, so elucidation of the physiological function of CTR will provide insights into the pathogenesis of ALS. The CTR has two Gly, aromatic, and Ser-rich (GaroS) segments and an amyloidogenic core divided into a hydrophobic patch (HP) and a Gln/Asn (Q/N)-rich segment. Although TDP-43 lacking the CTR is known to be unstable, as observed in knock-in mice, it is unclear which of these segments contributes to the stability of TDP-43. Here, we generated 12 mouse lines lacking the various sub-regions of CTR by genome editing and compared the embryonic lethality of homozygotes, and protein and mRNA expression levels of TDP-43. We demonstrated the functional diversity of the four segments of CTR, finding that the presence of the Q/N-rich segment greatly restored the protein stability of TDP-43. In addition, we found that the second GaroS deletion did not affect protein stability and mouse development.

    DOI: 10.1038/s41598-022-19153-0

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  • Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism. Reviewed International journal

    Yohko Yoshida, Ippei Shimizu, Atsuhiro Shimada, Keita Nakahara, Sachiko Yanagisawa, Minoru Kubo, Shinji Fukuda, Chiharu Ishii, Hiromitsu Yamamoto, Takamasa Ishikawa, Kuniyuki Kano, Junken Aoki, Goro Katsuumi, Masayoshi Suda, Kazuyuki Ozaki, Yutaka Yoshida, Shujiro Okuda, Shigeo Ohta, Shiki Okamoto, Yasuhiko Minokoshi, Kanako Oda, Toshikuni Sasaoka, Manabu Abe, Kenji Sakimura, Yoshiaki Kubota, Norihiko Yoshimura, Shingo Kajimura, Maria Zuriaga, Kenneth Walsh, Tomoyoshi Soga, Tohru Minamino

    Scientific reports   12 ( 1 )   14883 - 14883   2022.9

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    Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.

    DOI: 10.1038/s41598-022-19245-x

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  • Generation of Lungs by Blastocyst Complementation in Apneumic Fgf10-Deficient Mice Reviewed International journal

    Akihiko Kitahara, Qingsong Ran, Kanako Oda, Akihiro Yasue, Manabu Abe, Xulu Ye, Toshikuni Sasaoka, Masanori Tsuchida, Kenji Sakimura, Yoichi Ajioka, Yasuo Saijo, Qiliang Zhou

    CELL REPORTS   31 ( 6 )   107626 - 107626   2020.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CELL PRESS  

    The shortage of donor lungs hinders lung transplantation, the only definitive option for patients with endstage lung disease. Blastocyst complementation enables the generation of transplantable organs from pluripotent stem cells (PSCs) in animal models. Pancreases and kidneys have been generated from PSCs by blastocyst complementation in rodent models. Here, we report the generation of lungs using mouse embryonic stem cells (ESCs) in apneumic Fgf10 Ex1(mut)/Ex3(mut) mice by blastocyst complementation, Complementation with ESCs enables Fgf10-deficient mice to survive to adulthood without abnormalities, Both the generated lung alveolar parenchyma and the interstitial portions, including vascular endothelial cells, vascular and parabronchial smooth muscle cells, and connective tissue, largely originate from the injected ESCs. These data suggest that Fgf10 Ex1(mut)/Ex3(mut) blastocysts provide an organ niche for lung generation and that blastocyst complementation could be a viable approach for generating whole lungs.

    DOI: 10.1016/j.celrep.2020.107626

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  • Generation of Thyroid Tissues From Embryonic Stem Cells via Blastocyst Complementation In Vivo. Reviewed International journal

    Qingsong Ran, Qiliang Zhou, Kanako Oda, Akihiro Yasue, Manabu Abe, Xulu Ye, Yingchun Li, Toshikuni Sasaoka, Kenji Sakimura, Yoichi Ajioka, Yasuo Saijo

    Frontiers in endocrinology   11   609697 - 609697   2020

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    The generation of mature, functional, thyroid follicular cells from pluripotent stem cells would potentially provide a therapeutic benefit for patients with hypothyroidism, but in vitro differentiation remains difficult. We earlier reported the in vivo generation of lung organs via blastocyst complementation in fibroblast growth factor 10 (Fgf10), compound, heterozygous mutant (Fgf10 Ex1mut/Ex3mut) mice. Fgf10 also plays an essential role in thyroid development and branching morphogenesis, but any role thereof in thyroid organogenesis remains unclear. Here, we report that the thyroids of Fgf10 Ex1mut/Ex3mut mice exhibit severe hypoplasia, and we generate thyroid tissues from mouse embryonic stem cells (ESCs) in Fgf10 Ex1mut/Ex3mut mice via blastocyst complementation. The tissues were morphologically normal and physiologically functional. The thyroid follicular cells of Fgf10 Ex1mut/Ex3mut chimeric mice were derived largely from GFP-positive mouse ESCs although the recipient cells were mixed. Thyroid generation in vivo via blastocyst complementation will aid functional thyroid regeneration.

    DOI: 10.3389/fendo.2020.609697

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  • Nephrin-Binding Ephrin-B1 at the Slit Diaphragm Controls Podocyte Function through the JNK Pathway Reviewed International journal

    Yoshiyasu Fukusumi, Ying Zhang, Ryohei Yamagishi, Kanako Oda, Toru Watanabe, Katsuyuki Matsui, Hiroshi Kawachi

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   29 ( 5 )   1462 - 1474   2018.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC NEPHROLOGY  

    Background B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear.Methods We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy.Results Compared with controls, ephrin-B1 conditional knockout mice displayed altered podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Ephrin-B1 expressed in HEK293 cells immunoprecipitated with nephrin, which required the basal regions of the extracellular domains of both proteins. Treatment of cells with an anti-nephrin antibody promoted the phosphorylation of nephrin and ephrin-B1. However, phosphorylation of ephrin-B1 did not occur in cells expressing a mutant nephrin lacking the ephrin-B1 binding site or in cells treated with an Src kinase inhibitor. The phosphorylation of ephrin-B1 enhanced the phosphorylation of nephrin and promoted the phosphorylation of c-Jun N-terminal kinase (JNK), which was required for ephrin-B1-promoted cell motility in wound-healing assays. Notably, phosphorylated JNK was detected in the glomeruli of control mice but not ephrin-B1 conditional knockout mice. In rats, the phosphorylation of ephrin-B1, JNK, and nephrin occurred in the early phase (24 hours) of anti-nephrin antibody-induced nephropathy.Conclusions Through interactions with nephrin, ephrin-B1 maintains the structure and barrier function of the slit diaphragm. Moreover, phosphorylation of ephrin-B1 and, consequently, JNK are involved in the development of podocyte injury.

    DOI: 10.1681/ASN.2017090993

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  • Striatal hypodopamine phenotypes found in transgenic mice that overexpress glial cell line-derived neurotrophic factor Reviewed International journal

    Hidekazu Sotoyama, Yuriko Iwakura, Kanako Oda, Toshikuni Sasaoka, Nobuyuki Takei, Akiyoshi Kakita, Hideki Enomoto, Hiroyuki Nawa

    NEUROSCIENCE LETTERS   654   99 - 106   2017.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER IRELAND LTD  

    Glial cell line-derived neurotrophic factor (GDNF) positively regulates the development and maintenance of in vitro dopaminergic neurons. However, the in vivo influences of GDNF signals on the brain dopamine system are controversial and not fully defined. To address this question, we analyzed dopaminergic phenotypes of the transgenic mice that overexpress GDNF under the control of the glial Gfap promoter. Compared with wild-type, the GDNF transgenic mice contained higher levels of GDNF protein and phosphorylated RET receptors in the brain. However, there were reductions in the levels of tyrosine hydroxylase (TH), dopamine, and its metabolite homovanillic acid in the striatum of transgenic mice. The TH reduction appeared to occur during postnatal development. Immunohistochemistry revealed that striatal TH density was reduced in transgenic mice with no apparent signs of neurodegeneration. In agreement with these neurochemical traits, basal levels of extracellular dopamine and high K+-induced dopamine efflux were decreased in the striatum of transgenic mice. We also explored the influences of GDNF overexpression on lomomotor behavior. GDNF transgenic mice exhibited lower stereotypy and rearing in a novel environment compared with wild-type mice. These results suggest that chronic overexpression of GDNF in brain astrocytes exerts an opposing influence on nigrostriatal dopamine metabolism and neurotransmission. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.neulet.2017.06.005

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  • Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition Reviewed International journal

    Mie Naruse, Ryuichi Ono, Masahito Irie, Kenji Nakamura, Tamio Furuse, Toshiaki Hino, Kanako Oda, Misho Kashimura, Ikuko Yamada, Shigeharu Wakana, Minesuke Yokoyama, Fumitoshi Ishino, Tomoko Kaneko-Ishino

    DEVELOPMENT   141 ( 24 )   4763 - 4771   2014.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:COMPANY BIOLOGISTS LTD  

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposonderived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/ Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function.

    DOI: 10.1242/dev.114520

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  • Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex Reviewed International journal

    Takashi Namba, Yuji Kibe, Yasuhiro Funahashi, Shinichi Nakamuta, Tetsuya Takano, Takuji Ueno, Akiko Shimada, Sachi Kozawa, Mayumi Okamoto, Yasushi Shimoda, Kanako Oda, Yoshino Wada, Tomoyuki Masuda, Akira Sakakibara, Michihiro Igarashi, Takaki Miyata, Catherine Faivre-Sarrailh, Kosei Takeuchi, Kozo Kaibuchi

    NEURON   81 ( 4 )   814 - 829   2014.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CELL PRESS  

    The polarization of neurons, which mainly includes the differentiation of axons and dendrites, is regulated by cell-autonomous and non-cell-autonomous factors. In the developing central nervous system, neuronal development occurs in a heterogeneous environment that also comprises extracellular matrices, radial glial cells, and neurons. Although many cell-autonomous factors that affect neuronal polarization have been identified, the microenvironmental cues involved in neuronal polarization remain largely unknown. Here, we show that neuronal polarization occurs in a microenvironment in the lower intermediate zone, where the cell adhesion molecule transient axonal glycoprotein-1 (TAG-1) is expressed in cortical efferent axons. The immature neurites of multipolar cells closely contact TAG-1-positive axons and generate axons. Inhibition of TAG-1-mediated cell-to-cell interaction or its downstream kinase Lyn impairs neuronal polarization. These results show that the TAG-1-mediated cell-to-cell interaction between the unpolarized multipolar cells and the pioneering axons regulates the polarization of multipolar cells partly through Lyn kinase and Rac1.

    DOI: 10.1016/j.neuron.2013.12.015

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  • Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury Reviewed International journal

    Kosei Takeuchi, Nozomu Yoshioka, Susumu Higa Onaga, Yumi Watanabe, Shinji Miyata, Yoshino Wada, Chika Kudo, Masayasu Okada, Kentaro Ohko, Kanako Oda, Toshiya Sato, Minesuke Yokoyama, Natsuki Matsushita, Masaya Nakamura, Hideyuki Okano, Kenji Sakimura, Hitoshi Kawano, Hiroshi Kitagawa, Michihiro Igarashi

    NATURE COMMUNICATIONS   4   2740 - 2740   2013.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration-an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.

    DOI: 10.1038/ncomms3740

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  • TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding Reviewed International journal

    Mayumi Okamoto, Takashi Namba, Tomoyasu Shinoda, Takefumi Kondo, Tadashi Watanabe, Yasuhiro Inoue, Kosei Takeuchi, Yukiko Enomoto, Kumiko Ota, Kanako Oda, Yoshino Wada, Ken Sagou, Kanako Saito, Akira Sakakibara, Ayano Kawaguchi, Kazunori Nakajima, Taiji Adachi, Toshihiko Fujimori, Masahiro Ueda, Shigeo Hayashi, Kozo Kaibuchi, Takaki Miyata

    NATURE NEUROSCIENCE   16 ( 11 )   1556 - 1566   2013.11

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    Neural progenitors exhibit cell cycle-dependent interkinetic nuclear migration (INM) along the apicobasal axis. Despite recent advances in understanding its underlying molecular mechanisms, the processes to which INM contributes mechanically and the regulation of INM by the apicobasally elongated morphology of progenitors remain unclear. We found that knockdown of the cell-surface molecule TAG-1 resulted in retraction of neocortical progenitors' basal processes. Highly shortened stem-like progenitors failed to undergo basalward INM and became overcrowded in the periventricular (subapical) space. Surprisingly, the overcrowded progenitors left the apical surface and migrated into basal neuronal territories. These observations, together with the results of in toto imaging and physical tests, suggest that progenitors may sense and respond to excessive mechanical stress. Although, unexpectedly, the heterotopic progenitors remained stem-like and continued to sequentially produce neurons until the late embryonic period, histogenesis was severely disrupted. Thus, INM is essential for preventing overcrowding of nuclei and their somata, thereby ensuring normal brain histogenesis.

    DOI: 10.1038/nn.3525

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  • Point Mutation in Syntaxin-1A Causes Abnormal Vesicle Recycling, Behaviors, and Short Term Plasticity Reviewed International journal

    Yumi Watanabe, Norikazu Katayama, Kosei Takeuchi, Tetsuya Togano, Rieko Itoh, Michiko Sato, Maya Yamazaki, Manabu Abe, Toshiya Sato, Kanako Oda, Minesuke Yokoyama, Keizo Takao, Masahiro Fukaya, Tsuyoshi Miyakawa, Masahiko Watanabe, Kenji Sakimura, Toshiya Manabe, Michihiro Igarashi

    JOURNAL OF BIOLOGICAL CHEMISTRY   288 ( 48 )   34906 - 34919   2013.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Background: Roles of the syntaxin-1ACaMKII interaction are not physiologically understood in vivo.Results: A point mutation in syntaxin-1A caused abnormal plasticity, recycling, and behaviors in mice. Conclusion: The CaMKII/syntaxin-1A interaction is essential for maintenance of neuronal plasticity. Significance: Syntaxin-1A is involved in regulatory pathways in higher brain functions.Syntaxin-1A is a t-SNARE that is involved in vesicle docking and vesicle fusion; it is important in presynaptic exocytosis in neurons because it interacts with many regulatory proteins. Previously, we found the following: 1) that autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII), an important modulator of neural plasticity, interacts with syntaxin-1A to regulate exocytosis, and 2) that a syntaxin missense mutation (R151G) attenuated this interaction. To determine more precisely the physiological importance of this interaction between CaMKII and syntaxin, we generated mice with a knock-in (KI) syntaxin-1A (R151G) mutation. Complexin is a molecular clamp involved in exocytosis, and in the KI mice, recruitment of complexin to the SNARE complex was reduced because of an abnormal CaMKII/syntaxin interaction. Nevertheless, SNARE complex formation was not inhibited, and consequently, basal neurotransmission was normal. However, the KI mice did exhibit more enhanced presynaptic plasticity than wild-type littermates; this enhanced plasticity could be associated with synaptic response than did wild-type littermates; this pronounced response included several behavioral abnormalities. Notably, the R151G phenotypes were generally similar to previously reported CaMKII mutant phenotypes. Additionally, synaptic recycling in these KI mice was delayed, and the density of synaptic vesicles was reduced. Taken together, our results indicated that this single point mutation in syntaxin-1A causes abnormal regulation of neuronal plasticity and vesicle recycling and that the affected syntaxin-1A/CaMKII interaction is essential for normal brain and synaptic functions in vivo.

    DOI: 10.1074/jbc.M113.504050

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  • Accelerated modification of the zona pellucida is the primary cause of decreased fertilizability of oocytes in the 129 inbred mouse strain. Reviewed International journal

    Toshiaki Hino, Kanako Oda, Kenji Nakamura, Hiroyuki Tateno, Yutaka Toyoda, Minesuke Yokoyama

    Zygote (Cambridge, England)   19 ( 4 )   315 - 22   2011.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CAMBRIDGE UNIV PRESS  

    We investigated whether the small litter size in the 129 inbred mouse strain results from a reduction in oocyte fertilizability. Sensitivity of the zona pellucida to α-chymotrypsin was examined for oocytes collected at 14 h (shortly after ovulation), 17 h, and 20 h after hCG injection. Passage of spermatozoa through the zona pellucida (using an in vitro fertilization (IVF) technique) and the density of cortical granules were examined for oocytes collected at 14 and 17 h after hCG injection. The capability of the oolemma to fuse with the sperm plasma membrane was also evaluated by IVF using zona-free eggs. The zona pellucida became markedly resistant to the enzyme 17 h after hCG injection. IVF rates significantly decreased at this time. In addition, there was a significant reduction in the density of cortical granules. When zona-free oocytes were inseminated, high fertilization rates were obtained at both 17 and 14 h after hCG injection. These results indicate that accelerated modification of the zona pellucida primarily causes a decreased fertilizability of oocytes in 129 mice, resulting in the low reproductive performance of this strain.

    DOI: 10.1017/S0967199410000481

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  • Low fertility in vivo resulting from female factors causes small litter size in 129 inbred mice. Reviewed

    Toshiaki Hino, Kanako Oda, Kenji Nakamura, Yutaka Toyoda, Minesuke Yokoyama

    Reproductive medicine and biology   8 ( 4 )   157 - 161   2009.12

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    Purpose: 129 inbred mice show poor reproductive ability, as evidenced by small litters; however, the exact cause of this is unknown. In the present in vivo study we examined fertility and subsequent post-implantation development in an attempt to clarify the cause of small litter size in 129 mice. Methods: 129 or C57BL/6J females that displayed vaginal plugs 1 day after mating with males of the same strain were examined for the presence of fertilized eggs. Reciprocal matings were also performed between 129 and C57BL/6J mice. Subsequent post-implantation development of fertilized eggs was examined by dissecting females 18-19 days after the vaginal plugs were found. Results: Mean numbers of recovered eggs were 7.9 and 8.0 in 129 and C57BL/6J mice, respectively. Half of the recovered eggs were unfertilized in 129 mice, whereas all were fertilized in C57BL/6J mice. Mean numbers of live fetuses 18-19 days after mating were significantly lower in 129 mice (4.7) than in C57BL/6J mice (7.3). In different types of pairings using both strains of mice, the fertility was significantly lower whenever 129 females were used. Conclusions: The small litter size in 129 mice is caused by low fertility resulting from female factors.

    DOI: 10.1007/s12522-009-0024-y

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  • Marked Improvement of Fertility of Cryopreserved C57BL/6J Mouse Sperm by Depletion of Ca2+ in Medium Reviewed

    Rika Suzuki-Migishima, Toshiaki Hino, Miho Takabe, Kanako Oda, Fujio Migishima, Yoshiharu Morimoto, Minesuke Yokoyama

    JOURNAL OF REPRODUCTION AND DEVELOPMENT   55 ( 4 )   386 - 392   2009.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SOCIETY REPRODUCTION & DEVELOPMENT-SRD  

    Cryopreservation of mouse sperm is useful for maintaining various strains. However, fertility generally decreases after freezing. In particular, the fertility of cryopreserved C57BL/6J sperm is very low. To improve the fertility of frozen sperm, we examined the efficiencies of various media used for sperm preincubation (SP) and in vitro fertilization (IVF) in frozen C57BL/6J sperm. In this study, SP medium was examined for efficiency of fertility with respect to content, especially calcium (Ca2+), phosphate (PO43-) and lactate. In all media containing no Call, including medium lacking Ca2+, lacking Ca2+ and PO43- lacking Ca2+ and lactate and lacking Ca2+, PO43- and lactate, high IVF rates were obtained (79, 69, 76 and 71%, respectively). On the other hand, the rates for media containing Ca2+ were significantly lower (30-38%, P<0.05). After transfer, 41-50% of newborns were obtained in all media containing no Ca2+. In conclusion, preincubation of thawed sperm in medium containing no Ca2+ markedly improved the fertility of cryopreserved C57BL/6J sperm. These results indicate that the present method of IVF using medium with no Ca2+ is practical for use in cryopreserved C57BL/6J sperm.

    DOI: 10.1262/jrd.20163

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  • Paternal deletion of Meg1/Grb10 DMR causes maternalization of the Meg1/Grb10 cluster in mouse proximal Chromosome 11 leading to severe pre- and postnatal growth retardation Reviewed International journal

    Hirosuke Shiura, Kenji Nakamura, Takafusa Hikichi, Toshiaki Hino, Kanako Oda, Rika Suzuki-Migishima, Takashi Kohda, Tomoko Kaneko-Ishino, Fumitoshi Ishino

    HUMAN MOLECULAR GENETICS   18 ( 8 )   1424 - 1438   2009.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Mice with maternal duplication of proximal Chromosome 11 (MatDp(prox11)), where Meg1/Grb10 is located, exhibit pre- and postnatal growth retardation. To elucidate the responsible imprinted gene for the growth abnormality, we examined the precise structure and regulatory mechanism of this imprinted region and generated novel model mice mimicking the pattern of imprinted gene expression observed in the MatDp(prox11) by deleting differentially methylated region of Meg1/Grb10 (Meg1-DMR). It was found that Cobl and Ddc, the neighboring genes of Meg1/Grb10, also comprise the imprinted region. We also found that the mouse-specific repeat sequence consisting of several CTCF-binding motifs in the Meg1-DMR functions as a silencer, suggesting that the Meg1/Grb10 imprinted region adopted a different regulatory mechanism from the H19/Igf2 region. Paternal deletion of the Meg1-DMR (+/Delta DMR) caused both upregulation of the maternally expressed Meg1/Grb10 Type I in the whole body and Cobl in the yolk sac and loss of paternally expressed Meg1/Grb10 Type II and Ddc in the neonatal brain and heart, respectively, demonstrating maternalization of the entire Meg1/Grb10 imprinted region. We confirmed that the +/Delta DMR mice exhibited the same growth abnormalities as the MatDp(prox11) mice. Fetal and neonatal growth was very sensitive to the expression level of Meg1/Grb10 Type I, indicating that the 2-fold increment of the Meg1/Grb10 Type I is one of the major causes of the growth retardation observed in the MatDp(prox11) and +/Delta DMR mice. This suggests that the corresponding human GRB10 Type I plays an important role in the etiology of Silver-Russell syndrome caused by partial trisomy of 7p11-p13.

    DOI: 10.1093/hmg/ddp049

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  • 胚盤胞補完法を利用したマウスES細胞による肺再生

    北原 哲彦, 周 啓亮, 冉 慶松, 叶 許緑, 小田 佳奈子, 笹岡 俊邦, 阿部 学, 崎村 建司, 味岡 洋一, 泰江 章博, 土田 正則, 西條 康夫

    日本外科学会定期学術集会抄録集   118回   1340 - 1340   2018.4

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  • D1/D2ドーパミン受容体コンディショナル発現マウスによる運動制御機構の解明

    笹岡 俊邦, 佐藤 朝子, 知見 聡美, 大久保 直, 阿部 学, 川村 名子, 中尾 聡宏, 齊藤 奈英, 酒井 清子, 小田 佳奈子, 前田 宜俊, 神保 幸弘, 田中 稔, 山本 美丘, 佐藤 俊哉, 藤澤 信義, 崎村 建司, 南部 篤

    生命科学系学会合同年次大会   2017年度   [4LT08 - 1195)]   2017.12

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  • D1ドーパミン受容体を介するシグナルによる運動量の維持

    笹岡 俊邦, 佐藤 朝子, 知見 聡美, 大久保 直, 前島 純, 新井 慧, 砂山 智子[森田], 小田 佳奈子, 酒井 清子, 前田 宜俊, 神保 幸弘, 馬川 恵梨子, 佐藤 俊哉, 藤澤 信義, 横山 峯介, 南部 篤

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [3P1337] - [3P1337]   2015.12

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  • 【精神疾患動物モデルの可能性と課題】統合失調症モデルマウスの行動解析方法の試み

    笹岡 俊邦, 佐藤 朝子, 中村 徹, 大久保 直, 佐藤 俊哉, 藤澤 信義, 前田 宜俊, 小田 佳奈子, 酒井 清子, 神保 幸弘, 馬川 恵梨子, 木津川 尚史, 籾山 俊彦, 山森 哲雄

    日本生物学的精神医学会誌   26 ( 2 )   87 - 94   2015.6

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    統合失調症の疾患モデル動物の評価には、行動の変化を解析することが多いことから、行動解析法の妥当性の検討が必要である。疾患モデルとして遺伝子操作マウスは有用であるが、異なる研究室からの解析結果の再現性が課題であり、その解決は容易でない。例えばモデル動物の運動量評価のためには遺伝背景等を同一条件とし、かつ実験方法が同一であることが望ましい。本稿ではコンジェニック系統のドーパミン受容体遺伝子変異マウスを用いて、ホームケージにおける運動量・摂食量・飲水量の解析方法について我々が開発した実験方法を紹介する。今後、統合失調症の疾患モデル動物の新たな行動解析の方法として評価することを考えている。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J05574&link_issn=&doc_id=20150812470003&doc_link_id=%2Fcy8jbiop%2F2015%2F002602%2F004%2F0087-0094%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcy8jbiop%2F2015%2F002602%2F004%2F0087-0094%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • ポドサイト機能維持におけるEphrin B1の役割 KOマウスを用いた解析

    福住 好恭, 小田 佳奈子, 河内 裕

    日本腎臓学会誌   57 ( 3 )   566 - 566   2015.4

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  • 初期胚の体外培養がマウスの個体発生に及ぼす影響

    小田 佳奈子

    新潟医学会雑誌   128 ( 12 )   635 - 646   2014.12

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    Language:Japanese   Publisher:新潟医学会  

    【目的】生殖工学的操作はマウスの生産に広く活用されているが、私は、生殖工学的操作で欠かせない体外培養が初期胚の発生および個体発生に及ぼす影響を明確にするため、体外培養した初期胚の発生の早さ・細胞数・遺伝子発現の解析、および体外培養胚から生産した個体と自然交配で得た個体の主要な臓器重量の比較等の解析を行った。【方法と結果】マウス胚を組換えヒトアルブミン(r)を加えたrKSOMaa培地またはrMW培地で培養を行ったものを体外培養(In vitro)胚とし、偽妊娠マウスに移植を行ったものを母体内発生(In vivo)胚として解析を行った。In vitro胚とIn vivo胚の形態を比較した結果、胚盤胞期胚の形態の違いが観察され、In vitro rKSOMaa区およびIn vivo区では高率で胚盤胞期胚へと発生することが分かった。胚盤胞期胚への発生時期を解析したところ、In vitro rKSOMaa区はIn vitro rMW区より胚盤胞期胚への発生が早いことが観察され、培養培地の違いによっても発生率に違いが見られた。免疫抗体法を用いて簡便に媒精後96時間における内部細胞塊(ICM)および栄養外胚葉(TE)の細胞数を計数した結果、In vitro rKSOMaa区では、In vivo区に比較して、ICM数は少ない(p<0.05)が、TE数は多く(p<0.05)、総細胞数は同等であった。TUNEL法を用いてアポトーシス細胞数を計数した結果、In vitro rKSOMaa区およびIn vivo区と比較しIn vitro rMW区で多かった(p<0.05)。胚移植を行い、妊娠19.5日目における産仔への発生数と総着床数を計数した。In vitro rKSOMaa区では総着床数が多いにもかかわらず、In vivo区よりも産仔への発生数が低かった。In vitro rMW区は産仔率、総着床率共に低かった(p<0.05)。体重および臓器重量の比較した結果、出生後52週ではIn vitro rKSOMaa区で体重が重く、メスでは内臓以外の重量がオスでは内臓重量が多かった。インプリント遺伝子と分化マーカー遺伝子の発現解析では、In vitro rKSOMaa区ではIn vivo区に対して、インプリント遺伝子であるH19の発現は低かったが、一方、栄養外胚葉の分化マーカーであるCdxと未分化細胞マーカーであるNanogは有意に高い値を示した。【考察】マウス初期胚は体外培養を行うと、母体内培養を行ったものと比較し、胚の形態、発生時期並びに細胞数に差を生じ、産仔率の低下と成熟後の体重の増加という個体への発生に大きく影響を受ける事が示された。また、体外培養下で胚盤胞期におけるインプリント遺伝子の発現低下が確認された。このことは体外培養によりインプリント遺伝子のメチル化状態がリセットされていない部分があることを示唆している。【結論】体外培養胚は、母体内発生胚に比べて胚盤胞期胚へ高効率で早く発生するが、インプリント遺伝子および分化マーカー遺伝子の発現に変化が見られ、産仔率に差があった。また、体外培養胚由来の個体は、自然交配由来の個体に比べ、成熟期の体重・臓器重量が増加していた。本研究により、自然交配と同等の動物生産に向けて体外培養を最適化する指標が明らかとなった。(著者抄録)

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  • 人工制限酵素による内在性TDP-43遺伝子改変と筋萎縮性側索硬化症モデルへの応用

    佐藤 俊哉, 小田 佳奈子, 酒井 清子, 廣川 祥子, 永田 史也, 前田 宜俊, 藤澤 信義, 西澤 正豊, 小野寺 理, 横山 峯介

    臨床神経学   53 ( 12 )   1500 - 1500   2013.12

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  • 日本哺乳動物卵子学会によるヒト胚培地の開発 マウス胚による検討

    横山 峯介, 小田 佳奈子

    Journal of Mammalian Ova Research   29 ( 2 )   S8 - S8   2012.4

  • 129系マウス卵子における受精障害の原因の解明

    日野 敏昭, 小田 佳奈子, 中村 健司, 立野 裕幸, 豊田 裕, 横山 峯介

    Journal of Mammalian Ova Research   27 ( 2 )   S61 - S61   2010.4

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  • Study of small litter size in 129 mice

    HINO Toshiaki, ODA Kanako, NAKAMURA Kenji, TOYODA Yutaka, YOKOYAMA Minesuke

    26 ( 2 )   S78   2009.4

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  • 129系マウスにおける低い体外受精率の検討

    日野 敏昭, 小田 佳奈子, 横山 峯介

    日本生殖医学会雑誌   53 ( 4 )   269 - 269   2008.10

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  • ブタ顆粒膜細胞は種々の間葉系細胞に分化転換する

    小田 佳奈子, 加野 浩一郎

    日本発生生物学会大会講演要旨集   38回   240 - 240   2005.5

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  • ブタ顆粒膜細胞は種々の間葉系細胞に分化転換する

    小田 佳奈子, 遠藤 克, 加野 浩一郎

    日本畜産学会大会講演要旨集   104回   204 - 204   2005.3

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Research Projects

  • 嗅神経軸索におけるmRNA局所翻訳の機構と生理的意義の解明

    Grant number:22K06895

    2022.4 - 2025.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    福田 七穂, 小田 佳奈子

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

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  • Generation of purely pluripotent stem cell derived lung organ

    Grant number:21H02923

    2021.4 - 2024.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\16250000 ( Direct Cost: \12500000 、 Indirect Cost:\3750000 )

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  • 肺臓器移植を目指した異種間胚盤胞補完法による肺臓器創出と肺欠損大型モデルの開発

    Grant number:20H03741

    2020.4 - 2024.3

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

    周 ケイリョウ, 笹岡 俊邦, 土田 正則, 中務 胞, 小田 佳奈子, 泰江 章博

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

    本研究は、異種間胚盤胞補完法を用いて、異種間肺臓器作出方法技術の確立を目指すものである。まずは同種間においてはマウス生体内に肺臓器の作成を検証した。既に、肺臓器を欠損するFgf10 Ex1mut/Ex3mut マウスを開発し、胚盤胞補完法にてマウスの生体内にGFP陽性mES細胞に由来する機能的肺臓器の作出に成功した(Cell reports. 31(6):107626, 2020; Frontiers in Endocrinology. 2020 Dec 14;11:609697)。次に、異種間の設定でVenus陽性ラットES細胞を肺や気管が欠損するFgf10 Ex1mut/Ex3mutマウスの胚盤胞に移入し、マウス生体内にラットES細胞由来の肺臓器の作出を試みた。2020年度において、計6回、total500個超のマウス胚盤胞にラットES細胞のマイクロインジェクションを行い、インジェクションするラットES細胞の数や胚盤胞の時期等の条件につき検討した。2-5個程度のラットESを移植した場合のキメラ率がより高いことを示したが、依然として効率は低かった。また、新生児の異種間キメラマウスにおいて、四肢と肺の形成を認め、ラットES細胞によるレスキューを示した。ただし、新生児の組織解析においては、四肢欠損が十分にレスキューされていない場合があった。肺組織を用いて、肺臓器の各種細胞マーカーを使って免疫蛍光染色を行ったところ、一部にVenus陽性ラットES細胞由来組織を認めたが、キメラリズムは高くなかった。詳細な組織解析は進行中である。
    異種間胚盤胞補完法を用いて肺欠損マウスにおいてラットES細胞由来の肺臓器再生の可能性を示唆した。但し、効率は極めて低く、改良する必要がある。

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  • Effect of Octanoic acid and lipid metabolism in preembryo and pluripotent stem cells culture

    Grant number:15K10692

    2015.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    KUJI NAOAKI

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    It was demonstrated that commercially available human in-vitro fertilization medium had contained 500uM-1000uM octanoic acid, using mass spectrometric analysis. Using F1 and inbred mice in-vitro fertilized embryo, several effects were recognized in the medium containing 800 and 1200uM of OA ; 1) in vitro embryo development (up to blastocyst stage) were delayed and disturbed, 2) implantation rates were decreased and 3) body weight were decreased after 179days after birth. Gene expression analysis revealed that expression pattern were different in several genes, including imprinting genes.

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  • Searching genes regulating VWM disease severity.

    Grant number:15K06909

    2015.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Tsujita Mika, ODA Kanako, KITAURA Hiroki

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    Grant amount:\5070000 ( Direct Cost: \3900000 、 Indirect Cost:\1170000 )

    Vanishing white matter (VWM) disease is known to have a wide range of severity of, but the pathological determinants at the molecular level have not been clarified. In this study, we tried Quantitative trait locus (QTL) analysis and influence factor search using gene expression analysis using causative gene mutant mouse of VWM disease. In the genetic background of B6 and C3H strains, the difference in the start timings of walking abnormalities in mutant mice was evident, and as a result of QTL analysis using this as an indicator, correlated chromosomal regions were detected. In this region, several genes showed marked differences in expression levels (e.g., ion transporter and apolipoprotein related genes). This method will be useful for elucidating the molecular level of the pathology of VWM disease.

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  • GENERATION OF LUNG ORGAN FROM EMBRYONIC STEM CELLS VIA BLASTOCYST COMPLEMENTATION IN MIC

    Grant number:15K15320

    2015.4 - 2017.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    SAIJO YASUO, SAKIMURA KENJI, OHUCHI HIDEYO

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    Grant amount:\3510000 ( Direct Cost: \2700000 、 Indirect Cost:\810000 )

    We have developed Fgf10-/- mice by CRISPR/Cas system . Since the Fgf10-/- die immediately after birth, the Fgf10+/- genotype mice are maintained. We implanted 40 control embryos that was not injected ES cells into pseudopregnant mice and we obtained 13 littermates (32.5%) from the mice. 4 littermates (30.7%) showed limb defect (Fgf10-/-) and they were confirmed histologically that they had hypoplastic or aplastic lung. EGFPposotive ES cells were injected into blacystocyte of Fgf10-/- mice. 45 littermates were obtained from those mice. 38 littermates were EGFP positive. All EGFP positive mice showed the lung organ histologically. We sacrificed and analyzed histology in EGFP positive mice over one month. EGFP was positive in their lungs. The tissue, cells, and structure of their lung were well developed and not different from normal mice lung by H-E staining. Frozen section of the lung showed EGFP positive in alveolar epithelium, endothelium, tracheal cartilage.

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  • Technical development of transplantation human iPS induced hapatoblast and hepatocyte to mice embryos.

    Grant number:26640060

    2014.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    MORITA KUNIE

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    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    This research has conducrted 4 years, from fiscal year 2013 to 2017. The first year of this research, the research reader had changed the laboratory, from Kumamoto University to Niigata University of Health and Welfare. We were granted human iPS cells fron RIKEN, and we strarted differentiation- induced experiment from iPS cells to hepatocytes. And then, we confirmed differentiation to hepatocytes by means of immunological staining, hepatocyes marker ALB, SERPINA1 and HNF4A.
    This achivemnnt would help education and research for unversity students trying to be medical techcologysts, the reseach reader instructed there.

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  • Elucidation of motor control mechanism by D1 / D2 dopamine receptor conditionally expressing mice

    Grant number:26290029

    2014.4 - 2017.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    SASAOKA Toshikuni, NAKAO Satohiro, NAMBU Atsushi, CHIKEN Satomi

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    Grant amount:\16900000 ( Direct Cost: \13000000 、 Indirect Cost:\3900000 )

    Using genetically modified mice that reversibly suppress expression of dopamine D1 receptor (D1R) by drug (doxycycline) administration, D1R deficiency leads to decrease of motor activity. Normally, the electrical stimulation at motor cortex travels through three pathways (hyper-direct, direct and indirect pathways) and is recorded as neural activity of triphasic "excitation - suppression - excitement" in the entopeduncular nucleus, the output part of the basal ganglia. In the state of D1R deficiency, 'suppression' disappeared. It is believed that this "suppression" passes through the direct pathway of the basal ganglia circuit and works for induction of movement. In this study, information via D1R is thought to be indispensable for signaling of the direct pathway and induction of movement, and a decrease in the dynamic transmission of signals through the direct pathway is thought to lead to motor symptoms of Parkinson's disease.

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Teaching Experience (researchmap)