7 results on '"Takeda, Naoki"'
Search Results
2. Enhanced inhibitory neurotransmission in the cerebellar cortex of Atp1a3-deficient heterozygous mice
- Author
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Ikeda, Keiko, Satake, Shin'Ichiro, Onaka, Tatsushi, Sugimoto, Hiroki, Takeda, Naoki, Imoto, Keiji, and Kawakami, Kiyoshi
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Neurons ,Neuroscience: Neurobiology of Disease ,Mice, Transgenic ,In Vitro Techniques ,Motor Activity ,Synaptic Transmission ,Mice, Inbred C57BL ,Cerebellar Cortex ,Dystonia ,Mice ,Protein Subunits ,Interneurons ,Animals ,Sodium-Potassium-Exchanging ATPase ,Psychomotor Performance - Abstract
Dystonia is characterized by excessive involuntary and prolonged simultaneous contractions of both agonist and antagonist muscles. Although the basal ganglia have long been proposed as the primary region, recent studies indicated that the cerebellum also plays a key role in the expression of dystonia. One hereditary form of dystonia, rapid-onset dystonia with parkinsonism (RDP), is caused by loss of function mutations of the gene for the Na pump α3 subunit (ATP1A3). Little information is available on the affected brain regions and mechanism for dystonia by the mutations in RDP. The Na pump is composed of α and β subunits and maintains ionic gradients of Na(+) and K(+) across the cell membrane. The gradients are utilized for neurotransmitter reuptake and their alteration modulates neural excitability. To provide insight into the molecular aetiology of RDP, we generated and analysed knockout heterozygous mice (Atp1a3(+/-)). Atp1a3(+/-) showed increased symptoms of dystonia that is induced by kainate injection into the cerebellar vermis. Atp1a3 mRNA was highly expressed in Purkinje cells and molecular-layer interneurons, and its product was concentrated at Purkinje cell soma, the site of abundant vesicular γ-aminobutyric acid transporter (VGAT) signal, suggesting the presynaptic localization of the α3 subunit in the inhibitory synapse. Electrophysiological studies showed that the inhibitory neurotransmission at molecular-layer interneuron-Purkinje cell synapses was enhanced in Atp1a3(+/-) cerebellar cortex, and that the enhancement originated via a presynaptic mechanism. Our results shed light on the role of Atp1a3 in the inhibitory synapse, and potential involvement of inhibitory synaptic dysfunction for the pathophysiology of dystonia.
- Published
- 2013
3. Administration of factor XIII B subunit increased plasma factor XIII A subunit levels in factor XIII B subunit knock-out mice.
- Author
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Souri, Masayoshi, Koseki-Kuno, Shiori, Takeda, Naoki, Degen, Jay, Ichinose, Akitada, and Degen, Jay L
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RECOMBINANT proteins ,ANIMAL experimentation ,BIOLOGICAL models ,BLOOD coagulation factors ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,MICE ,RESEARCH ,EVALUATION research ,THERAPEUTICS - Abstract
Factor XIII (FXIII) is a proenzyme of plasma transglutaminase consisting of enzymatic A (FXIII-A) and noncatalytic B subunits (FXIII-B), and acts in hemostasis and wound healing. We freshly generated mice lacking either FXIII-A or FXIII-B to investigate the physiological functions of FXIII in vivo. Mice carrying the disrupted allele were born at the expected Mendelian ratios, and the homozygous mice were viable and fertile under specific pathogen-free conditions. Although all homozygous and heterozygous mice showed no marked difference from the wild-type animals in general appearance, homozygous mice of either FXIII-A- or FXIII-B-deficiency did have prolonged bleeding times. It was confirmed that thrombin-dependent amine incorporation and fibrin-crosslinking in plasma were undetectable in the FXIII-A-deficient mice and markedly reduced in the FXIII-B-deficient mice; however, the gene expression of each subunit was regulated independently. Recombinant human FXIII-B (rFXIII-B) was expressed in a baculovirus expression system. When rFXIII-B was injected into FXIII-B-deficient mice, FXIII-A levels, fibrin crosslinking, and amine-incorporation activities increased in their plasma, indicating that FXIII-B assisted the maintenance of FXIII-A levels in the circulation. These mouse strains will be useful in exploring the possible pathophysiological roles of each subunit in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
4. Abnormalities Caused by Carbohydrate Alterations in Iβ6 -N-Acetylglucosaminyltransferase-Deficient Mice.
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Guo-Yun Chen, Muramatsu, Hisako, Kondo, Mineo, Kurosawa, Nobuyuki, Miyake, Yozo, Takeda, Naoki, and Muramatsu, Takashi
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CARBOHYDRATES ,IMMUNE system ,LEUCOCYTES ,EPITHELIAL cells ,MICE ,KIDNEYS - Abstract
Iβ6-N-acetylglucosaminyltransferase (IGnT) catalyzes the branching of poly-N-acetyllactosamine carbohydrate chains. In both humans and mice, three spliced forms of IGnT have been identified, and a common exon is present in all of them. We generated mice deficient in the common exon to understand the physiological function of poly-N-acetyllactosamine branching. IGnT activity was abolished in the stomach, kidney, bone marrow, and cerebellum of the deficient mice, while a low level of the activity persisted in the small intestine. Immunohistochemical analysis confirmed the loss of I antigen from the lung, stomach, and kidney. The deficient mice had reduced spontaneous locomotive activity. The number of peripheral blood lymphocytes was also reduced and renal function decreased in the deficient mice. Furthermore, in aged mice, vacuolization occurred in the kidney, and epidermoid cysts were frequently formed. However, cataracts did not develop earlier in the deficient mice. Decreased levels of lysosomal proteins, LAMP-2 and synaptotagmin VII, were found in the kidney of the deficient mice and correlated with renal abnormalities. [ABSTRACT FROM AUTHOR]
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- 2005
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5. Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAT-1) Is Required for Branching Morphogenesis in the Chorioallantoic Placenta.
- Author
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Tanaka, Hiroyuki, Nagaike, Koki, Takeda, Naoki, Itoh, Hiroshi, Kohama, Kazuyo, Fukushima, Tsuyoshi, Miyata, Shiro, Uchiyama, Shuichiro, Uchinokura, Shunro, Shimomura, Takeshi, Miyazawa, Keiji, Kitamura, Naomi, Yamada, Gen, and Kataoka, Hiroaki
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GROWTH factors ,CYTOKINES ,PEPTIDES ,MICE ,MOLECULAR biology ,CYTOLOGY - Abstract
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-associated Kunitz-type serine proteinase inhibitor that was initially identified as a potent inhibitor of hepatocyte growth factor activator. HAI-1 is also a cognate inhibitor of matriptase, a membrane-associated serine proteinase. HAI-1 is expressed predominantly in epithelial cells in the human body. Its mRNA is also abundant in human placenta, with HAI-1 specifically expressed by villous cytotrophoblasts. In order to address the precise roles of HAI-1 in vivo, we generated HAI-1 mutant mice by homozygous recombination. Heterozygous HAI-1
+/- mice underwent normal organ development. However, homozygous HAI-1-/- mice experienced embryonic lethality which became evident at embryonic day 10.5 postcoitum (E10.5). As early as E9.5, HAI-1-/- embryos showed growth retardation that did not reflect impaired cell proliferation but resulted instead from failed placental development and function. Histological analysis revealed severely impaired formation of the labyrinth layer, in contrast all other placental layers, such as the spongiotrophoblast layer and giant cell layer, which were formed. Our results indicate that mouse HAI-1 is essential for branching morphogenesis in the chorioallantoic placenta and lack of HAI-1 function may result in placental failure. [ABSTRACT FROM AUTHOR]- Published
- 2005
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6. Expression of Tom34 Splicing Isoforms in Mouse Testis and Knockout of Tom34 in Mice.
- Author
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Terada, Kazutoyo, Ueno, Shota, Yomogida, Kentaro, Imai, Tomoaki, Kiyonari, Hiroshi, Takeda, Naoki, Yano, Masato, Abe, Shinichi, Aizawa, Shinichi, and Mori, Masataka
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LABORATORY mice ,PROTEINS ,POLYMERASE chain reaction ,GENOMICS ,MESSENGER RNA - Abstract
The 34-kDa translocase of the outer mitochondrial membrane (Tom34) is a putative mammalian-specific factor involved in protein import into mitochondria. We analyzed the genomic sequence of the mouse Tom34 gene and found it has two alternative initial exons. Using reverse transcription and the polymerase chain reaction (RT-PCR), we found that these two mRNAs differs only in the 5′-proximal sequences corresponding to the two initial exons (exon 1a and 1b). Tom34 mRNA with exon 1a (Tom34a) is expressed ubiquitously, while that with exon 1b (Tom34b) is expressed only in mature testicular germ cells. To explore the in vivo function of Tom34 proteins, we generated Tom34-deficient mice by targeted disruption. The Tom34–/– mice were viable and grew normally and had a normal Mendelian inheritance pattern. Male as well as female Tom34–/– mice were fertile. In vitro-preprotein import into isolated mitochondria showed no apparent difference between Tom34–/– and wild-type mice. These results indicate that Tom34 is dispensable for mouse growth and development under optimal conditions. [ABSTRACT FROM PUBLISHER]
- Published
- 2003
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7. Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities.
- Author
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Yamazaki, Satoru, Iwalnoto, Ryo, Saeki, Kazuko, Asakura, Masanori, Takashimia, Seiji, Yamazaki, Ayano, Kimura, Rina, Mizushima, Hiroto, Moribe, Hiroki, Higashiyama, Shigeki, Endoh, Masayuki, Kaneda, Yasufwmi, Takagi, Satoshi, Itami, Satoshi, Takeda, Naoki, Yamada, Gen, and Mekada, Eisuke
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HUMAN abnormalities , *HEART failure , *HYPERPLASIA , *MICE - Abstract
Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HB[SUPuc]) or a transmembrane domain-truncated form (HB&[SUPDelta]tm) of the molecule. HB[SUPuc/uc]mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HB[SUPΔtm] exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
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