共查询到20条相似文献,搜索用时 15 毫秒
1.
Ikumi Katano Ryoji Ito Tsutomu Kamisako Tomoo Eto Tomoyuki Ogura Kenji Kawai Hiroshi Suemizu Takeshi Takahashi Yutaka Kawakami Mamoru Ito 《Experimental Animals》2014,63(3):321-330
We have developed NOD-Rag2null IL-2Rγnull (NR2G)
mice similar to NOD-scidIL-2Rγnull (NOG) mice
that are known as an excellent host to generate humanized mice. To evaluate the usefulness
of NR2G mice as a host for humanized mice, the engraftment rates and differentiation of
human cells after human hematopoietic stem cell (HSC) transplantation were compared among
NR2G, NOG, and NOD-scid mice. For this purpose, the appropriate
irradiation doses to expand the niche for human stem cells in the bone marrow were first
determined. As a result, 8 and 2.5 Gy in adult, and 4 and 1 Gy in newborn NR2G and NOG
mice, respectively, were found to be appropriate. Next, 5 × 104 human umbilical
cord blood CD34+ cells were intravenously inoculated into irradiated adult or
newborn of the immunodeficient mice. These HSC transplantation experiments demonstrated
that both NR2G and NOG mice showed high engraftment rates compared with
NOD-scid mice, although NOG mice showed a slightly higher engraftment
rate than that for NR2G mice. However, no difference was found in the human cell
populations differentiated from HSCs between NR2G and NOG mice. The HSC transplantation
experiments to adults and newborns of two immunodeficient mice also revealed that the HSC
transplantation into newborn mice resulted in higher engraftment rate than those into
adults. These results showed that NR2G mice could be used as an alternative host to NOG
mice to generate humanized mice. 相似文献
2.
3.
Otto Kalliokoski Kirsten R. Jacobsen Huda S. Darusman Trine Henriksen Allan Weimann Henrik E. Poulsen Jann Hau Klas S. P. Abelson 《PloS one》2013,8(3)
The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology. 相似文献
4.
Sara Dolatshahi Pirooz Joo-Hyung Lee Zhen Zhao Duojiao Ni Soohwan Oh Chengyu Liang 《Journal of visualized experiments : JoVE》2011,(57)
γ-Herpesviruses (γ-HVs) are notable for their ability to establish latent infections of lymphoid cells1. The narrow host range of human γ-HVs, such as EBV and KSHV, has severely hindered detailed pathogenic studies. Murine γ-herpesvirus 68 (γHV68) shares extensive genetic and biological similarities with human γ-HVs and is a natural pathogen of murid rodents2. As such, evaluation of γHV68 infection of mice inbred strains at different stages of viral infection provides an important model for understanding viral lifecycle and pathogenesis during γ-HVs infection.Upon intranasal inoculation, γHV68 infection results in acute viremia in the lung that is later resolved into a latent infection of splenocytes and other cells, which may be reactivated throughout the life of the host3,4. In this protocol, we will describe how to use the plaque assay to assess infectious virus titer in the lung homogenates on Vero cell monolayers at the early stage (5 - 7 days) of post-intranasal infection (dpi). While acute infection is largely cleared 2 - 3 weeks postinfection, a latent infection of γHV68 is established around 14 dpi and maintained later on in the spleen of the mice. Latent infection usually affects a very small population of cells in the infected tissues, whereby the virus stays dormant and shuts off most of its gene expression. Latently-infected splenocytes spontaneously reactivate virus upon explanting into tissue culture, which can be recapitulated by an infectious center (IC) assay to determine the viral latent load. To further estimate the amount of viral genome copies in the acutely and/or latently infected tissues, quantitative real-time PCR (qPCR) is used for its maximal sensitivity and accuracy. The combined analyses of the results of qPCR and plaque assay, and/or IC assay will reveal the spatiotemporal profiles of viral replication and infectivity in vivo.Download video file.(81M, mov) 相似文献
5.
Franck Duclos Volker Straub Steven A. Moore David P. Venzke Ron F. Hrstka Rachelle H. Crosbie Madeleine Durbeej Connie S. Lebakken Audrey J. Ettinger Jack van der Meulen Kathleen H. Holt Leland E. Lim Joshua R. Sanes Beverly L. Davidson John A. Faulkner Roger Williamson Kevin P. Campbell 《The Journal of cell biology》1998,142(6):1461-1471
Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the α-sarcoglycan gene. To determine how α-sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed α-sarcoglycan– deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of α-sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of α-dystroglycan association with membranes. In contrast, no change in the expression of ε-sarcoglycan (α-sarcoglycan homologue) was observed. Recombinant α-sarcoglycan adenovirus injection into Sgca-deficient muscles restored the sarcoglycan complex and sarcospan to the membrane. We propose that the sarcoglycan–sarcospan complex is requisite for stable association of α-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease. 相似文献
6.
Adam D. Bachstetter Scott J. Webster Tao Tu Danielle S. Goulding Jacques Haiech D. Martin Watterson Linda J. Van Eldik 《PloS one》2014,9(8)
The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, β, δ, γ), with CaMKIIα and CaMKIIβ highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIβ isoform. We report the development and extensive behavioral and phenotypic characterization of a CaMKIIβ knockout (KO) mouse. The CaMKIIβ KO mouse was found to be smaller at weaning, with an altered body mass composition. The CaMKIIβ KO mouse showed ataxia, impaired forelimb grip strength, and deficits in the rotorod, balance beam and running wheel tasks. Interestingly, the CaMKIIβ KO mouse exhibited reduced anxiety in the elevated plus maze and open field tests. The CaMKIIβ KO mouse also showed cognitive impairment in the novel object recognition task. Our results provide a comprehensive behavioral characterization of mice deficient in the β isoform of CaMKII. The neurologic phenotypes and the construction of the genotype suggest the utility of this KO mouse strain for future studies of CaMKIIβ in brain structure, function and development. 相似文献
7.
8.
Recently, aluminum (Al) has been identified as one of the environmental factors responsible for cause certain nerve degeneration
diseases, particularly, Alzheimer’s disease (AD). However, the relationship between Al and AD is controversial. We previously
examined whether Al induced neurotoxin in the brain of mice when aluminum–maltolate complex (ALM) was administered daily for
120 days. Our results revealed that Al accumulated in the brain induced oxidative stress, and the nerve degeneration was detected
in the brain of the ALM-treated group. On the basis of these results, we have tried to examine whether the incorporated Al
affects memory in mice with regard to an indicator of spatial memory deficits depending on the chemical forms of Al, namely,
as an ion (AlCl3) and in the form of a complex (ALM). We administered saline, AlCl3, and ALM at a concentration of 40 μmol Al/kg body weight to mice by daily ip injections for 60 days. We assessed spatial memory by a water maze task and determined the Al levels in the brain of the
mice by the neutron activation analysis method. Spatial memory deficit as an indicator of the swimming time was related to
Al accumulation in the brain of mice; the chemical form of the Al compound was important in order to exhibit the memory deficit
in mice; the uptake of Al is higher in mice when it is administered in a complex form than in an ionic form. 相似文献
9.
10.
The development of the mammalian skull is a complex process that requires multiple tissue interactions and a balance of growth and differentiation. Disrupting this balance can lead to changes in the shape and size of skull bones, which can have serious clinical implications. For example, insufficient ossification of the bony elements leads to enlarged anterior fontanelles and reduced mechanical protection of the brain. In this report, we find that loss of Gsk3β leads to a fully penetrant reduction of frontal bone size and subsequent enlarged frontal fontanelle. In the absence of Gsk3β the frontal bone primordium undergoes increased cell death and reduced proliferation with a concomitant increase in Fgfr2-IIIc and Twist1 expression. This leads to a smaller condensation and premature differentiation. This phenotype appears to be Wnt-independent and is not rescued by decreasing the genetic dose of β-catenin/Ctnnb1. Taken together, our work defines a novel role for Gsk3β in skull development. 相似文献
11.
Maria Shirely Herbas Mototada Shichiri Noriko Ishida Aiko Kume Yoshihisa Hagihara Yasukazu Yoshida Hiroshi Suzuki 《PloS one》2015,10(8)
The emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. Recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. However, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. Here, we report on a new strategy to potentially treat malaria by using probucol, a drug that can reduce the plasma α-tocopherol concentration. Probucol pre-treatment for 2 weeks and treatment throughout the infection rescued from death of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition, survival was extended when the treatment started immediately after parasite inoculation. The ratio of lipid peroxidation products to parent lipids increased in plasma after 2 weeks treatment of probucol. This indicates that the protective effect of probucol might be mediated by the oxidative stressful environment induced by α-tocopherol deficiency. Probucol in combination with dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results indicated that probucol might be a candidate for a drug against malaria infection by inducing α-tocopherol deficiency without dietary α-tocopherol restriction. 相似文献
12.
Hitoshi Ando Hayato Yanagihara Koh‐ichi Sugimoto Yohei Hayashi Shuichi Tsuruoka Toshinari Takamura 《Chronobiology international》2013,30(4):655-665
Recent studies have shown the gene expression of several transporters to be circadian rhythmic. However, it remains to be elucidated whether the expression of P‐glycoprotein, which is involved in the transport of many medications, undergoes 24 h rhythmicity. To address this issue, we investigated daily profiles of P‐glycoprotein mRNA and protein levels in peripheral mouse tissues. In the liver and intestine, but not in the kidney, Abcb1a mRNA expression showed clear 24 h rhythmicity. On the other hand, Abcb1b and Abcb4, the other P‐glycoprotein genes, did not exhibit significant rhythmic expression in the studied tissues. In the intestine, levels of whole P‐glycoprotein also exhibited a daily rhythm, with a peak occurring in the latter half of the light phase and a trough at the onset of the light phase. Consistent with the day‐night change of P‐glycoprotein level, the ex vivo accumulation of digoxin, an Abcb1a P‐glycoprotein substrate, into the intestinal segments at the onset of dark phase was significantly lower than it was at the onset of the light phase. Thus, Abcb1a P‐glycoprotein expression, and apparently its function, are 24 h rhythmic at least in mouse intestine tissue. This circadian variation might be involved in various chronopharmacological phenomena. 相似文献
13.
14.
The serine-threonine protein kinase Akt2, also known as PKBβ, has been shown to regulate glucose and lipid metabolism in animal models. In a recent study published in Science, Hussain et al. (2011) report that in human subjects an activating mutation of Akt2 leads to hypoglycemia and, unexpectedly, asymmetric overgrowth. 相似文献
15.
Bo Li Yunhe Zhao Hui Liu Bin Meng Jitao Wang Tianjun Qi Hui Zhang Tao Li Peiqing Zhao Hui Sun Jia Xu Haibo Song Zhe Dong Fengshuang An 《PloS one》2016,11(2)
Objectives
Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored.Methods
In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E–deficient (ApoE−/−) mice, and lentivirus expressing visfatin (lenti-visfatin) was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC) and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated.Results
Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production.Conclusions
Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index. 相似文献16.
Zhenshan Wang Vicky Li Guy C. K. Chan Trongha Phan Aaron S. Nudelman Zhengui Xia Daniel R. Storm 《PloS one》2009,4(9)
Background
A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time.Methodology/Principal Findings
We discovered that AC3−/− mice become obese as they age. Adult male AC3−/− mice are about 40% heavier than wild type male mice while female AC3−/− are 70% heavier. The additional weight of AC3−/− mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3−/− mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3−/− mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis.Conclusions/Significance
We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight. 相似文献17.
18.
Marvin Sommer Shannon Taylor Stacey Leisenfelder Robert Morton Ann Arvin Jennifer Moffat 《中国实验动物学报》2005,(Z1)
Human cytomegalovirus(HCMV)and Varicella Zoster virus(VZV)are belongto herpesvirusfamily.HCMVrarelycaus-es symptomatic diseaseinanimmunocompetent host;however,itis a major cause of infectious morbidityand mortalityinimmunocompromised individuals and developingfetuses.VZVinfectioncauses chickenpoxandshingles.Sincethese spe-cies-specific herpesviruses do notinfect other animals,noanimal model is availablefor pathogenesis studies.Severe com-binedimmunodeficient(SCID)mice implanted with hu… 相似文献
19.
20.
Jennifer Keiser Jacques Chollet Shu-Hua Xiao Jin-Yan Mei Pei-Ying Jiao Jürg Utzinger Marcel Tanner 《PLoS neglected tropical diseases》2009,3(1)