排序方式: 共有17条查询结果,搜索用时 15 毫秒
11.
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
12.
Tarragona M Pavlovic M Arnal-Estapé A Urosevic J Morales M Guiu M Planet E González-Suárez E Gomis RR 《The Journal of biological chemistry》2012,287(25):21346-21355
Metastasis requires numerous biological functions that jointly provide tumor cells from a primary site to seed and colonize a distant organ. Some of these activities are selected for in the primary site, whereas others are acquired at the metastatic niche. We provide molecular evidence showing that the BMP inhibitor, NOG, provides metastatic breast cancer cells with the ability to colonize the bone. NOG expression is acquired during the late events of metastasis, once cells have departed from the primary site, because it is not enriched in primary tumors with high risk of bone relapse. On the contrary, breast cancer bone metastatic lesions do select for high levels of NOG expression when compared with metastasis to the lung, liver, and brain. Pivotal to the bone colonization functions is the contribution of NOG to metastatic autonomous and nonautonomous cell functions. Using genetic approaches, we show that when NOG is expressed in human breast cancer cells, it facilitates bone colonization by fostering osteoclast differentiation and bone degradation and also contributes to metastatic lesions reinitiation. These findings reveal how aggressive cancer cell autonomous and nonautonomous functions can be mechanistically coupled to greater bone metastatic potential. 相似文献
13.
Establishment of a new model of human multiple myeloma using NOD/SCID/gammac(null) (NOG) mice 总被引:3,自引:0,他引:3
Miyakawa Y Ohnishi Y Tomisawa M Monnai M Kohmura K Ueyama Y Ito M Ikeda Y Kizaki M Nakamura M 《Biochemical and biophysical research communications》2004,313(2):258-262
We developed a new experimental animal model of human multiple myeloma using immunodeficient NOD/SCID/gammac(null) (NOG) mice. A human myeloma cell line, U266, was intravenously inoculated into 20 NOG mice, all of which developed hind leg paralysis and distress around 6 weeks after transplantation. Pathological studies showed that only the bone marrow was infiltrated with U266 cells, and no cells were present in other organs. Osteolytic lesions in cortical bones and loss of trabecular bones were prominent in U266-transplanted NOG mice. In contrast, U266 cells were not detected in CB17scid or NOD/SCID mice 6 weeks after intravenous inoculation. Human IgE, produced by U266 cells, was detected in the serum of U266-transplanted NOG mice by ELISA. The results indicated that this hu-myeloma NOG model might be useful for studying the pathogenesis of myeloma and related osteolytic lesions, and are suggestive of its applicability to the future development of new drugs. 相似文献
14.
Etsuko Fujii Atsuhiko Kato Yu Jau Chen Koichi Matsubara Yasuyuki Ohnishi Masami Suzuki 《Experimental Animals》2014,63(3):289-296
Human tumor tissue line models established in the severely immunodeficient
NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic
(NOD/Shi-scid, IL-2Rγnull or NOG) mouse are important tools
for oncology research. During the establishment process, a lymphoproliferative lesion
(LPL) that replaces the original tumor cells in the site of transplantation occurs. In the
present study, we studied the impact of the LPL on the establishment process and the
characteristics of the lesion, investigated the systemic distribution of the lesion in the
mouse, and evaluated the potential of a simple identification method. The incidence of the
lesion varied among tumor types, and the lesion was found to be the leading cause of
unsuccessful establishment with gastric and colorectal cancer. The lesion consisted of a
varying population of proliferating lymphoid cells that expressed CD20. The cells were
positive for Epstein-Barr virus (EBV)-related antigens, and EBV DNA was detected. There
was systemic distribution of the lesion within the NOG mouse, and the most consistent
gross finding was splenomegaly. Additionally, identification of LPL-affected cases was
possible by detecting splenomegaly in the 1st and 2nd generation mice at necropsy. From
our findings the lesion was judged to arise from EBV-infected B cells originating from the
donor, and monitoring splenomegaly at necropsy was thought effective as a simple method
for identifying the lesion at an early stage of the establishment process. 相似文献
15.
Recent reports have provided evidence that the β-hydroxylation of conserved asparaginyl residues in ankyrin repeat domain (ARD) proteins is a common posttranslational modification in animal cells. Here, nuclear magnetic resonance (NMR) and other biophysical techniques are used to study the effect of asparaginyl β-hydroxylation on the structure and stability of ‘consensus’ ARD proteins. The NMR analyses support previous work suggesting that a single β-hydroxylation of asparagine can stabilize the stereotypical ARD fold. A second asparaginyl β-hydroxylation causes further stabilization. In combination with mutation studies, the biophysical analyses reveal that the stabilizing effect of β-hydroxylation is, in part, mediated by a hydrogen bond between the asparaginyl β-hydroxyl group and the side chain of a conserved aspartyl residue, two residues to the N-terminal side of the target asparagine. Removal of this hydrogen bond resulted in reduced stabilization by hydroxylation. Formation of the same hydrogen bond is also shown to be a factor in inhibiting binding of hydroxylated ARDs to factor-inhibiting hypoxia-inducible factor (FIH). The effects of hydroxylation appear to be predominantly localized to the target asparagine and proximal residues, at least in the consensus ARD protein. The results reveal that thermodynamic stability is a factor in determining whether a particular ARD protein is an FIH substrate; a consensus ARD protein with three ankyrin repeats is an FIH substrate, while more stable consensus ARD proteins, with four or five ankyrin repeats, are not. However, NMR studies reveal that the consensus protein with four ankyrin repeats is still able to bind to FIH, suggesting that FIH may interact in cells with natural ankyrin repeats without resulting hydroxylation. Overall, the work provides novel biophysical insights into the mechanism by which asparaginyl β-hydroxylation stabilizes the ARD proteins and reduces their binding to FIH. 相似文献
16.
Monica Mantri Eleanor A. Bagg Danica S. Butler Kathryn L. Kavanagh Udo Oppermann Michael A. McDonough Christopher J. Schofield 《Journal of molecular biology》2010,401(2):211-2031
Lysyl and prolyl hydroxylations are well-known post-translational modifications to animal and plant proteins with extracellular roles. More recent work has indicated that the hydroxylation of intracellular animal proteins may be common. JMJD6 catalyses the iron- and 2-oxoglutarate-dependent hydroxylation of lysyl residues in arginine-serine-rich domains of RNA-splicing-related proteins. We report crystallographic studies on the catalytic domain of JMJD6 in complex with Ni(II) substituting for Fe(II). Together with mutational studies, the structural data suggest how JMJD6 binds its lysyl residues such that it can catalyse C-5 hydroxylation rather than N?-demethylation, as for analogous enzymes. 相似文献
17.