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1.
Tissue-specific replicating capacity of a chimeric poliovirus that carries the internal ribosome entry site of hepatitis C virus in a new mouse model transgenic for the human poliovirus receptor 下载免费PDF全文
Yanagiya A Ohka S Hashida N Okamura M Taya C Kamoshita N Iwasaki K Sasaki Y Yonekawa H Nomoto A 《Journal of virology》2003,77(19):10479-10487
Nucleotides (nt) 108 to 742 of an infectious cDNA clone of poliovirus (PV) Mahoney strain, including the corresponding region of the internal ribosome entry site (IRES), was replaced by nt 28 to 710 of hepatitis C virus (HCV) cDNA corresponding to the whole HCV IRES. A chimeric PV (2A-369) was generated by transfecting mammalian cells with an RNA transcribed in vitro from the cDNA. To examine replicating capacity of virus 2A-369 in the brain and liver of a mouse model for poliomyelitis, a new mouse model (MPVRTg25-61) that is transgenic for human PV receptor (hPVR; CD155) was generated in order to obtain a higher expression level of hPVR in the liver than those of hPVRTg mouse lines generated by us so far. The transgene used was constructed by combining a putative regulatory region of the mouse PVR homolog and the whole structural region of the hPVR gene. Virus 2A-369 replicated well in the liver of MPVRTg25-61 but not in the brain, whereas control Mahoney virus replicated well both in the liver and in the brain. The data suggest that the HCV IRES works more efficiently in the liver than in the brain and that PV IRES works well both in the liver and in the brain. The results support the notion that tissue-specific activity of IRES may be reflected in tissue tropism of a virus whose specific translation initiation is driven by IRES, that is, an IRES-dependent virus tropism. 相似文献
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Nishio M Watanabe K Sasaki J Taya C Takasuga S Iizuka R Balla T Yamazaki M Watanabe H Itoh R Kuroda S Horie Y Förster I Mak TW Yonekawa H Penninger JM Kanaho Y Suzuki A Sasaki T 《Nature cell biology》2007,9(1):36-44
Proper neutrophil migration into inflammatory sites ensures host defense without tissue damage. Phosphoinositide 3-kinase (PI(3)K) and its lipid product phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) regulate cell migration, but the role of PtdIns(3,4,5)P(3)-degrading enzymes in this process is poorly understood. Here, we show that Src homology 2 (SH2) domain-containing inositol-5-phosphatase 1 (SHIP1), a PtdIns(3,4,5)P(3) phosphatase, is a key regulator of neutrophil migration. Genetic inactivation of SHIP1 led to severe defects in neutrophil polarization and motility. In contrast, loss of the PtdIns(3,4,5)P(3) phosphatase PTEN had no impact on neutrophil chemotaxis. To study PtdIns(3,4,5)P(3) metabolism in living primary cells, we generated a novel transgenic mouse (AktPH-GFP Tg) expressing a bioprobe for PtdIns(3,4,5)P(3.) Time-lapse footage showed rapid, localized binding of AktPH-GFP to the leading edge membrane of chemotaxing ship1(+/+)AktPH-GFP Tg neutrophils, but only diffuse localization in ship1(-/-)AktPH-GFP Tg neutrophils. By directing where PtdIns(3,4,5)P(3) accumulates, SHIP1 governs the formation of the leading edge and polarization required for chemotaxis. 相似文献
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Suzuki T Kanai Y Hara T Sasaki J Sasaki T Kohara M Maehama T Taya C Shitara H Yonekawa H Frohman MA Yokozeki T Kanaho Y 《Molecular and cellular biology》2006,26(16):6149-6156
The mammalian small GTPase ADP-ribosylation factor 6 (ARF6) plays important roles in a wide variety of cellular events, including endocytosis, actin cytoskeletal reorganization, and phosphoinositide metabolism. However, physiological functions for ARF6 have not previously been examined. Here, we described the consequence of ARF6 ablation in mice, which manifests most obviously in the context of liver development. Livers from ARF6-/- embryos are smaller and exhibit hypocellularity, due to the onset of midgestational liver cell apoptosis. Preceding the apoptosis, however, defective hepatic cord formation is observed; the liver cells migrate abnormally upon exiting the primordial hepatic epithelial sheet and clump rather than becoming dispersed. Consistent with this observation, the ability of hepatocyte growth factor/scatter factor (HGF) to induce hepatic cord-like structures from ARF6-/- fetal hepatocytes cultured in vitro in collagen gel matrix is impaired. Finally, we show that endogenous ARF6 in wild-type fetal hepatocytes is activated in response to HGF stimulation. These results provide evidence that ARF6 is an essential component in the signaling pathway coupling HGF signaling to hepatic cord formation. 相似文献
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Takada T Shitara H Matsuoka K Kojima E Ishii R Kikkawa Y Taya C Karasuyama H Kohno K Yonekawa H 《Transgenic research》2008,17(6):1155-1162
Current mouse models for atopic dermatitis (AD) have a serious drawback, being the existence of dense hair on the body. Thus,
a hairless animal model on an AD-prone genetic background will be a powerful tool to investigate the basis of and therapy
for this complex disease. We applied the Toxin Receptor-mediated Cell Knockout (TRECK) method to generate a hairless transgenic
(Tg) mice on the NC/Nga background, an AD-prone inbred strain. A minigene with the mouse Keratin71 (Krt71) promoter and human diphtheria toxin receptor, which intrinsically functions as the heparin-binding EGF-like growth factor,
was introduced into the pronucleus of NC/Nga oocytes. Unexpectedly NCN24, one NC/Nga Tg line, showed a dominant hairless phenotype
without diphtheria toxin administration. Furthermore, the atopic dermatitis-like predisposition and IgE elevation was observed
in both NCN24 and the NC/Nga wildtype strain. NCN24 mice, which we have newly developed, will be useful to assess drugs for
AD therapy, being able to monitor skin inflammation without shaving.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
7.
FIKSEL (1988) provides an asymptotically unbiased kernel estimator for the density hs (r) of the spherical contact distribution function of stationary and isotropic point processes. This paper proposes alternative estimators of hs (r) for use with regular grid of locations. The existing estimator of hs (r) and the alternatives proposed in this paper are then tested out in a simulation study. 相似文献
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Takaki Fukuizumi Hiromasa Inoue Yuichi Anzai Toshiyuki Tsujisawa Choji Uchiyama 《Microbiology and immunology》1995,39(5):351-359
We have shown that the palatine tonsil effectively incorporates exogenous foreign substances instilled at its surface. It is not clear whether antigen-specific IgA can be induced by the instillation. Sheep red blood cells (SRBC) were instilled at the palatine tonsil every three days as the antigen, and the agglutination titer of specific IgA in saliva was examined. Nasal or intragastric administration, which have been shown to induce specific antibody in saliva, were done as control experiments. Anti-SRBC antibody in saliva from the tonsillar instillation group was detected in the second week, and the agglutination titer reached a maximum in the 6th week after the instillation. The maximum titers in the tonsillar instillation group and nasal administration group were 16 (P<0.01, n=7) and 4 times (P<0.01, n = 7) higher, respectively, than that in the intragastric administration group. In the tonsillar instillation group, the number of specific antibody-producing cells per 105 lymphocytes was the highest in the parotid glands compared with the lymphoid tissues such as the retropharyngeal lymph nodes, nasal mucosa, mesenteric lymph nodes, Peyer's patches, cervical lymph nodes, palatine tonsil and spleen. In the nasal administration group, the number of lymphocytes was the highest in the nasal mucosa. The results indicate that tonsillar instillation was more effective than nasal administration in inducing specific IgA in saliva. 相似文献
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Sari SUZUKI Masashi ISHIKAWA Takuya UEDA Yasuhiro OHSHIBA Yuki MIYASAKA Kazuhiro OKUMURA Michinari YOKOHAMA Choji TAYA Kunie MATSUOKA Yoshiaki KIKKAWA 《Experimental Animals》2015,64(3):241-251
The DBA/2J strain is a model for early-onset, progressive hearing loss in humans, as
confirmed in the present study. DBA/2J mice showed progression of hearing loss to
low-frequency sounds from ultrasonic-frequency sounds and profound hearing loss at all
frequencies before 7 months of age. It is known that the early-onset hearing loss of
DBA/2J mice is caused by affects in the ahl
(Cdh23ahl) and ahl8
(Fscn2ahl8) alleles of the cadherin 23 and fascin 2 genes,
respectively. Although the strong contributions of the
Fscn2ahl8 allele were detected in hearing loss at 8- and
16-kHz stimuli with LOD scores of 5.02 at 8 kHz and 8.84 at 16 kHz, hearing loss effects
were also demonstrated for three new quantitative trait loci (QTLs) for the intervals of
50.3–54.5, 64.6–119.9, and 119.9–137.0 Mb, respectively, on chromosome 5, with significant
LOD scores of 2.80–3.91 for specific high-frequency hearing loss at 16 kHz by quantitative
trait loci linkage mapping using a (DBA/2J × C57BL/6J) F1 × DBA/2J backcross
mice. Moreover, we showed that the contribution of Fscn2ahl8
to early-onset hearing loss with 32-kHz stimuli is extremely low and raised the
possibility of effects from the Cdh23ahl allele and another
dominant quantitative trait locus (loci) for hearing loss at this ultrasonic frequency.
Therefore, our results suggested that frequency-specific QTLs control early-onset hearing
loss in DBA/2J mice. 相似文献
10.
Mutsumi Yokota Hiroshi Shitara Osamu Hashizume Kazuto Nakada Choji Taya Hiromichi Yonekawa 《FEBS letters》2010,584(18):3943-3948
To investigate the effects of respiration defects on the disease phenotypes, we generated trans-mitochondrial mice (mito-mice) by introducing a mutated G13997A mtDNA, which specifically induces respiratory complex I defects and metastatic potentials in mouse tumor cells. First, we obtained ES cells and chimeric mice containing the G13997A mtDNA, and then we generated mito-mice carrying the G13997A mtDNA via its female germ line transmission. The three-month-old mito-mice showed complex I defects and lactate overproduction, but showed no other phenotypes related to mitochondrial diseases or tumor formation, suggesting that aging or additional nuclear abnormalities are required for expression of other phenotypes. 相似文献