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Construction of pINC-lacZ Retroviral Vector and its Expression in Mouse Embryonic Stem Cells
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作者 何维 吴鹤龄 《Developmental and Reproductive Biology》 1996年第1期1-6,共6页
A retroviral vector pINC-lacZ containing an E coli β-galactosidase(β-gal)gene was constructed and introduced into the MESPU-13 cells by electroporation.Four G418-resistant colonies were obtained from 1×107,elec... A retroviral vector pINC-lacZ containing an E coli β-galactosidase(β-gal)gene was constructed and introduced into the MESPU-13 cells by electroporation.Four G418-resistant colonies were obtained from 1×107,electroporated MESPU-13 cells. Histochemical staining for β-gal activity showed that lacZ gene was expressed in at least three of the four colonies.Southern analysis proved that one copy of foreign gene was integrated in the chromosome of one of the transformed lines(MC15).These results showed that the expression of lacZ gene driven by SiCMVIE promoter can be detected in the transformed MESPU-13 cells. 展开更多
关键词 ELECTROPORATION Transgenic mouse pINC-LacZ Retroviral Vector β-galactosidase gene
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Comparative study of histopathology changes between the PS1/APP double transgenic mouse model and Aβ_(1-40)-injected rat model of Alzheimer disease 被引量:7
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作者 Da-Bing LI Jun TANG +3 位作者 Xiao-Tang FAN Min SONG Hai-Wei XU Yun BAI 《Neuroscience Bulletin》 SCIE CAS CSCD 2006年第1期52-57,共6页
Objective To identify the genetype of the PS1/APP double transgenie mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenie mice models and Aβ1-40-in... Objective To identify the genetype of the PS1/APP double transgenie mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenie mice models and Aβ1-40-injeeted rats models of Alzheimer disease. Methods The modified congo red staining, Nissl's staining and immunohistology staining was used to observe the Aβ deposits, activation of astrocyte respectively. Results ①The PS1/APP transgenic mouse extensively displayed Aβ deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. ②The Aβ1-40-intrahippocmnpal-injeeted rat model showed the Aβ plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neurons loss was significant in the injection point and pin hole of injection with Nissl's staining methods. GFAP-positive cells increased significantly compared with the uninjected lateral of the hippocampus. Conclusion Although Aβ1-40-injected rat models could simulate some characteristic pathological features of human Alzheimer diseases, Aβ deposits and neurons loss in partial hippocampal, it would not simulate the progressive degenenration in the brain of AD. The double transgenie PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, mainly is Aβ deposits and the spongiocyte response , while no neurons loss were observed in this model. 展开更多
关键词 Alzheimer disease transgenic mouse RAT Β-AMYLOID
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Designing and generating a mouse model:frequently asked questions 被引量:3
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作者 Channabasavaiah BGurumurthy Thomas LSaunders Masato Ohtsuka 《The Journal of Biomedical Research》 CAS CSCD 2021年第2期76-90,共15页
Genetically engineered mouse(GEM)models are commonly used in biomedical research.Generating GEMs involve complex set of experimental procedures requiring sophisticated equipment and highly skilled technical staff.Beca... Genetically engineered mouse(GEM)models are commonly used in biomedical research.Generating GEMs involve complex set of experimental procedures requiring sophisticated equipment and highly skilled technical staff.Because of these reasons,most research institutes set up centralized core facilities where custom GEMs are created for research groups.Researchers,on the other hand,when they begin thinking about generating GEMs for their research,several questions arise in their minds.For example,what type of model(s)would be best useful for my research,how do I design them,what are the latest technologies and tools available for developing my model(s),and finally how to breed GEMs in my research.As there are several considerations and options in mouse designs,and as it is an expensive and time-consuming endeavor,careful planning upfront can ensure the highest chance of success.In this article,we provide brief answers to several frequently asked questions that arise when researchers begin thinking about generating mouse model(s)for their work. 展开更多
关键词 CRISPR transgenic mouse genetic engineering knockout mouse conditional knockout mouse knock-in mouse
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Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models 被引量:1
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作者 Guanqun Qiao Qingquan Li +3 位作者 Gang Peng Jun Ma Hongwei Fan Yingbin Li 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第25期2360-2369,共10页
Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mou... Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc/SV40Tag+/Tet-on+) to explore the malignant trans- formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells. 展开更多
关键词 neural regeneration stem cells neural stern cells brain tumor stem cells subventricular zone braintumor transgenic mouse model multidirectional differentiation DOXYCYCLINE NEUROREGENERATION
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TGF-beta1 Transgenic Mouse Model of Thoracic Irradiation: Modulation of MMP-2 and MMP-9 in the Lung Tissue 被引量:1
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作者 杨坤禹 刘莉 +4 位作者 张涛 伍钢 Ruebe Claudia Ruebe Christian 胡豫 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2006年第3期301-304,共4页
To investigate the effects of TGF-β1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-β1 were measured with western blot, and e... To investigate the effects of TGF-β1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-β1 were measured with western blot, and expressions of MMP-2 and MMP-9 were analyzed with zymography in a TGF-β1 transgenic mouse model after thoracic irradiation with 12 Gy. We found expressions of TGF-β1 in the lung from the transgenic mice were three folds as compared to those from control mice. With densitometrical analysis, we found a significant decrease in MMP-9 activity in lung homogenates from the transgenic mice as compared with those from non-transgenic control mice 8 weeks after sham-irradiation (relative MMP-9 activity: C: 1. 000±0. 1091; TG: 0. 4772±0. 470 (n=8, P〈0.05). But MMP-2 was constitutively expressed in the lung homogenates from the transgenic mice as compared to those from control mice 8 weeks after sham-irradiation (relative MMP-2 activity 8 weeks after sham-irradiation: C: 1. 000±0. 1556, TG: 1. 0075±0. 1472). Eight weeks after thoracic irradiation with 12 Gy, we observed a significant increase of MMP-2 and MMP-9 activity in lung homogenates from both transgenic and normal mice. In TGF-β1 transgenic mice relative MMP-9 activity was increased to 1. 5321±0. 2217 folds 8 weeks after thoracic irradiation with 12 Gy as compared to those after sham-irradiation (1. 000±0. 2153), and relative MMP-2 activity was increased to 1. 7142 ± 0. 4231 folds. Our results show that TGF-β1 itself down-regulates activity of MMP-9, thereby decreases ECM degradation in lungs of TGF-β1 transgenic mice. Also we find that ionizing irradiation upregulates both MMP-2 and MMP-9 activity. Over-expressions of MMP-9 and MMP-2 after lung irradiation are involved in the inflammatory response associated with radiation-induced lung injury, and maybe further in radiation-induced lung fibrosis. 展开更多
关键词 TGF-β1 transgenic mouse metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs)
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INFLUENCE OF CHEMOTHERAPEUTANTS AND CYTOKINES ONGROWTH AND TRANSGENE EXPRESSION OF BONE MARROWCELLS FROM MT/P210^(bcr-ab1) TRANSGENIC MICE
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作者 陈汉春 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1999年第4期245-248,共4页
Objective: To investigate the influcnce ofchemotherapeutic agents and cytokines on growth ofbone marrow cells from MT/p210 her-ab1 transgenic mice.Methods: The bone marrow cells of transgenic chronicmyelogenous leukem... Objective: To investigate the influcnce ofchemotherapeutic agents and cytokines on growth ofbone marrow cells from MT/p210 her-ab1 transgenic mice.Methods: The bone marrow cells of transgenic chronicmyelogenous leukemia (CML) model mice carryingmetallothionein (MT) promoter/enhancer, her-abl (p210)cDNA and SV40 splicinglpoly (A) signal sequences werecultured in liquid and soft agar with hydroxyurea (Hu),5-nuorouracil (5-Fu), mouse stem cell factor (mSCF)and mouse interleukin-3 (mIL-3) independently orcollectively. The cells and colonies were counted. Thelevels of transgene expression were detected by reversetranscriptase-polymerase chain reaction (RT-PCR).Results: The cell proliferation, colony formation andtransgene expression of the bone marrow cells werestimulated with mSCF and mIL-3, but there was littlegrowth without any growth factors, or when mSCF,mIL-3 and Hu or 5-Fu were added. Conclusion: Thecombined utilization of chemotherapeutants andcytokines is a potentially effective strategy of clinicaltreatment for CML. 展开更多
关键词 Gene ABL Transgenic mouse Chemotherapeutant mSCF mIL-3
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Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand 被引量:16
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作者 JIAHUAHU JIEJIANG +5 位作者 YINGHUAMA NAYANG MAOHUZHANG MINWU JIANFEI LIHEGUO 《Cell Research》 SCIE CAS CSCD 2003年第5期361-368,共8页
It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing hu... It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT)mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times.After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITCconjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice. 展开更多
关键词 Fas ligand ETHANOL APOPTOSIS TESTES transgenic mouse.
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Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis 被引量:2
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作者 Agata Bartczak Jianhua Zhang +6 位作者 Oyedele Adeyi Achiya Amir David Grant Reginald Gorczynski Nazia Selzner Andrzej Chruscinski Gary A Levy 《World Journal of Gastroenterology》 SCIE CAS 2017年第15期2673-2684,共12页
AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODS... AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODSTreg and Teff cells from fgl2<sup>-/-</sup>, fgl2<sup>+/+</sup>, and fgl2<sup>Tg</sup> mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1<sup>-/-</sup> mice.RESULTSIn vitro, fgl2<sup>Tg</sup> Treg had enhanced immunosuppressive activity, and fgl2<sup>Tg</sup> Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2<sup>+/+</sup>) into Rag1<sup>-/-</sup> mice produced both clinical and histologic colitis with dense infiltrates of CD3<sup>+</sup> T cells, crypt abscesses and loss of goblet cells. Fgl2<sup>Tg</sup> Treg prevented the development of T cell-induced colitis, whereas fgl2<sup>+/+</sup> and fgl2<sup>-/-</sup> Treg were only partially protective. In mice that received fgl2<sup>Tg</sup> Treg, the ratio of Foxp3<sup>+</sup> to CD3<sup>+</sup> cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2<sup>Tg</sup> mice did not produce colitis.CONCLUSIONHere we show that fgl2<sup>Tg</sup> Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2<sup>Tg</sup> Treg prevent colitis in contrast to fgl2<sup>+/+</sup> Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease. 展开更多
关键词 Fibrinogen-like protein 2 COLITIS Regulatory T cells Transgenic mouse Inflammatory bowel disease
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Advances in prostate cancer research models:From transgenic mice to tumor xenografting models 被引量:3
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作者 Yuejiao Huang Chun Cheng +4 位作者 Chong Zhang Yonghui Zhang Miaomiao Chen Douglas W.Strand Ming Jiang 《Asian Journal of Urology》 2016年第2期64-74,共11页
The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the re... The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the recent establishment of several transgenicmouse lines and/or xenografting models is better reflecting the disease in vivo.With appropriate models,valuable tools for elucidating the functions of specific genes have gone deep into prostate development and carcinogenesis.In the present review,we summarize a number of important PCa research models established in our laboratories(PSA-Cre-ERT2/PTEN transgenic mouse models,AP-OX model,tissue recombination-xenografting models and PDX models),which represent advances of translational models from transgenic mouse lines to human tumor xenografting.Better understanding of the developments of these models will offer new insights into tumor progression and may help explain the functional significance of genetic variations in PCa.Additionally,this understanding could lead to new modes for curing PCa based on their particular biological phenotypes. 展开更多
关键词 Prostate cancer Transgenic mouse lines Tumor xenografting models Translational medical systems
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Bcl-2 in suppressing neuronal apoptosis after spinal cord injury 被引量:6
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作者 Ying Wang Zhi-yang Sun +2 位作者 Kui-ming Zhang Guo-qiang Xu Guang Li 《World Journal of Emergency Medicine》 CAS 2011年第1期38-44,共7页
BACKGROUND: Apoptosis plays an important role in central neural diseases and trauma. B-cell lymphoma/Leukemia-2 (Bcl-2) can inhibit apoptosis in a wide variety of cells including neurons. In this experiment, by stu... BACKGROUND: Apoptosis plays an important role in central neural diseases and trauma. B-cell lymphoma/Leukemia-2 (Bcl-2) can inhibit apoptosis in a wide variety of cells including neurons. In this experiment, by studying Bcl-2 over-expression transgenic (TG) mice subjected to spinal cord injury (SCI), we investigated whether Bcl-2 could reduce posttraumatic neuronal apoptosis, reduce the range of damage, and improve the behavioral functional recovery after contusive SCI.METHODS: Nine Bcl-2 TG mice and nine control mice were subjected to SCI of moderate severity at T10, with the use of weight dropping (WD) method (impact force 2.5×3.0 g/cm). At times up to 1 day, 7 days and 14 days after SCI, functional defi cits were evaluated with Basso, Beattie, and Bresnahan (BBB) scales, and apoptosis of neurons was investigated by using the TUNEL method. Another three control mice only underwent lamina opening, but were not subjected to SCI, to provide blank comparison.RESULTS: The mean functional scores for the control mice (5.05 ±0.35) were lower than those for the Bcl-2 TG mice (5.45 ±0.15), although the unpaired T-test revealed no signifi cant difference (P=0.67). On the other hand, the number of TUNEL positive neurons and integrated option density (IOD) scores for the Bcl-2 TG mice were both signifi cantly lower than those for the control mice (P〈0.05).CONCLUSIONS: This experiment suggests that overexpression of Bcl-2 may suppress neuronal apoptosis after SCI. Bcl-2 may be an important factor within the central nervous system that can relieve the damage after trauma. 展开更多
关键词 Spinal cord injury BCL-2 Apoptosis of neurons Weight dropping Transgenic mouse
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Near infra-red light treatment of Alzheimer's disease 被引量:2
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作者 Mengmeng Han Qiyan Wang +5 位作者 Xue Wang Yuhui Zeng Yong Huang Qingqiang Meng Jun Zhang Xunbin Wei 《Journal of Innovative Optical Health Sciences》 SCIE EI CAS 2018年第1期57-64,共8页
Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No... Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No ffective treatments are available for AD,currently.Currenttreatments only attenuate symptoms temporarily and are associated with severe side ffects.Nearinfra-red(NIR)light has been studied for a long time.We investigated the effect of NIR on ADusing a transgenic mouse model,which was obtained by co-injecting two vectors carrying ADmutations in amyloid precursor protein(APP)and presenilin-i(PSEN1)into C57BL/6J mice.The irradiation equipment consisted of an accommodating box and an LED array.The wave-length of NIR light emitted from LED was between 1040 nm and 1090 nm.The power densitydelivered at the level of the mice was approximately 15 mW/cm^(2),Firstly,we treated the micewith NIR for 40 days,Then,the irradiation was suspended for 28 days.Finally,another 15 daystreatment was brought to mice.We conducted Morris water maze and immunofluorescenceanalysis to evaluate the effects of treatment.Immunofuorescence analysis was based on mea-suring the quantity of plaques in mouse brain slices,Our results show that NIR light improvesmemory and spatial learning ability and reduces plaques moderately.NIR light represents apotential treatment for AD. 展开更多
关键词 Alzheimer's disease near infra-red light transgenic mouse model Moris water maze immunofluorescence analysis
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Targeted expression of human FSH receptor Asp567Gly mutant mRNA in testis of transgenic mice: role of humanFSH receptor promoter 被引量:1
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作者 Verena Nordhoff Jrg Gromoll +6 位作者 Luca Foppiani C.Marc Luetjens Stefan Schlatt Elena Kostova Ilpo Huhtaniemi Eberhard Nieschlag Manuela Simoni 《Asian Journal of Andrology》 SCIE CAS CSCD 2003年第4期267-275,共9页
Aim: To specifically express the Asp567Gly human follicle-stimulating hormone receptor (FSHR) under the control of its promoter to evaluate the phenotypic consequences in the presence of normal pituitary function. Met... Aim: To specifically express the Asp567Gly human follicle-stimulating hormone receptor (FSHR) under the control of its promoter to evaluate the phenotypic consequences in the presence of normal pituitary function. Methods: We produced transgenic mice overexpressing the Asp567Gly human FSHR under the control of a 1.5kb 5' flanking region fragment of its promoter. Results: Mice were phenotypically normal and fertile. In males, mRNA could be detected in the testis and the brain, indicating that the 1.5kb promoter fragment drives expression not only in the gonads. The testis weight/body weight ratio and the testosterone levels in transgenic and non-transgenic litter mates were similar. By in situ hybridisation we found that the transgenic FSHR was highly expressed in Sertoli cells, spermatocytes and round spermatids. However, a radioligand receptor assay failed to show a significant difference in total FSHR binding sites in testis homogenates of transgenic and wild type animals, suggesting that the transgenic FSHR is probably not translated into functional receptor protein. Conclusion: A 1.5kb 5 '-region of the human FSHR drives mRNA expression of the transgene in the testis but leads to ectopic expression in germ cells and in the brain. No phenotypic consequences could be documented due to the lack of protein expression. 展开更多
关键词 transgenic mouse follicle-stimulating hormone receptor PROMOTER activating mutation Sertoli cells
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Collagen1α1 promoter drives the expression of Cre recombinase in osteoblasts of transgenic mice 被引量:1
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作者 Lagabaiyila Zha Ning Hou +4 位作者 Jian Wang Guan Yang Yuanrong Gao Lin Chen Xiao Yang 《Journal of Genetics and Genomics》 SCIE CAS CSCD 北大核心 2008年第9期525-530,共6页
Osteoblasts participate in bone formation, bone mineralization, osteoclast differentiation and many pathological processes. To study the function of genes in osteoblasts using Cre-LoxP system, we generated a mouse lin... Osteoblasts participate in bone formation, bone mineralization, osteoclast differentiation and many pathological processes. To study the function of genes in osteoblasts using Cre-LoxP system, we generated a mouse line expressing the Cre recombinase under the control of the rat Collagenlcd (Collα1) promoter (Collα1-Cre). Two founders were identified by genomic PCR from 16 offsprings, and the integration efficiency is 12.5%. In order to determine the tissue distribution and the activity of Cre recombinase in the transgenic mice, the Coll αl-Cre transgenic mice were bred with the ROSA26 reporter strain and a mouse strain that carries Smad4 conditional alleles (Smad4^Co/Co). Multiple tissue PCR of Collα1-Cre;Smad4^Co/+ mice revealed the restricted Cre activity in bone tissues containing osteoblasts and tendon. LacZ staining in the Collα1-Cre;ROSA26 double transgenic mice revealed that the Cre recombinase began to express in the osteoblasts of calvaria at E14.5. Cre activity was observed in the osteoblasts and osteocytes of P10 double transgenic mice. All these data indicated that the Collα1-Cre transgenic mice could serve as a valuable tool for osteoblast lineage analysis and conditional gene knockout in osteoblasts. 展开更多
关键词 Collagenl OSTEOBLAST Cre recombinase transgenic mouse
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Transgenic mice overexpressingγ-aminobutyric acid transporter subtypeⅠ develop obesity 被引量:1
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作者 MA YING HUA JIA HUA HU +5 位作者 XIAO GANG ZHOU RUO WANG ZENG ZHEN TONG MEI JIAN FEI LI HE GUO Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, China Shanghai Institute of 《Cell Research》 SCIE CAS CSCD 2000年第4期303-310,共8页
Transgenic mice ubiquitously overexpressing murine γ aminobutyric acid transporter subtype Ⅰ were created. Unexpectedly, these mice markedly exhibited heritable obesity, which features significantly increased body w... Transgenic mice ubiquitously overexpressing murine γ aminobutyric acid transporter subtype Ⅰ were created. Unexpectedly, these mice markedly exhibited heritable obesity, which features significantly increased body weight and fat deposition. Behavioral examination revealed that transgeinc mice have slightly reduced spontaneous locomotive capacity and altered feeding pattern. Tills preliminary finding indicates that the inappropriate level of γ-aminobutyric acid transporters may be directly or indirectly involved in the pathogenic mechanism underlying certain types of obesity. 展开更多
关键词 γ-aminobutyric acid transporter subtype transgenic mouse obesit€
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BACE1 in the retina:a sensitive biomarker for monitoring early pathological changes in Alzheimer's disease 被引量:1
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作者 Lan Li Jia Luo +8 位作者 Dan Chen Jian-bin Tong Le-ping Zeng Yan-qun Cao Jian Xiang Xue-gang Luo Jing-ming Shi Hui Wang Ju-fang Huang 《Neural Regeneration Research》 SCIE CAS CSCD 2016年第3期447-453,共7页
Because of a lack of sensitive biomarkers,the diagnosis of Alzheimer's disease(AD) cannot be made prior to symptom manifestation.Therefore,it is crucial to identify novel biomarkers for the presymptomatic diagnosis... Because of a lack of sensitive biomarkers,the diagnosis of Alzheimer's disease(AD) cannot be made prior to symptom manifestation.Therefore,it is crucial to identify novel biomarkers for the presymptomatic diagnosis of AD.While brain lesions are a major feature of AD,retinal pathological changes also occur in patients.In this study,we investigated the temporal changes in β-site APP-cleaving enzyme 1(BACE1) expression in the retina and brain to determine whether it could serve as a suitable biomarker for early monitoring of AD.APP/PS-1 transgenic mice,3,6 and 8 months of age,were used as an experimental group,and age-matched C57/BL6 wild-type mice served as the control group.In the Morris water maze test,there were no significant differences in escape latency or in the number of crossings in the target area among mice of different ages.Compared with wild-type mice,no changes in learning or memory abilities were detected in transgenic mice at 3 months of age.However,compared with wild-type mice,the escape latency was significantly increased in transgenic mice at 6 months,starting on day 3,and at 8 months,starting on day 2,during Morris water maze training.In addition,the number of crossings of the target area was significantly decreased in transgenic mice.The learning and memory abilities of transgenic mice were further worsened at 8 months of age.Immunohistochemical staining revealed no BACE1 plaques in wild-type mice at 3,6 or 8 months or in transgenic mice at 3 months,but they were clearly found in the entorhinal cortex,hippocampus and prefrontal cortex of transgenic mice at 6 and 8 months.BACE1 expression was not detected in the retina of wild-type mice at 3 months,but weak BACE1 expression was detected in the ganglion cell layer,inner plexiform layer and outer plexiform layer at 6 and 8 months.In transgenic mice,BACE1 expression in the ganglion cell layer was increased at 3 months,and BACE1 expression in the ganglion cell layer,inner plexiform layer and outer plexiform layer was significantly increased at 6 and 8 months,compared with age-matched wild-type mice.Taken together,these results indicate that changes in BACE1 expression appear earlier in the retina than in the brain and precede behavioral deficits.Our findings suggest that abnormal expression of BACE1 in the retina is an early pathological change in APP/PS-1 transgenic mice,and that BACE1 might have potential as a biomarker for the early diagnosis of AD in humans. 展开更多
关键词 nerve regeneration neurodegenerative disease Alzheimer's disease retina amyloid-β β-site amyloid precursor protein cleaving enzyme 1 APP/PS-1 transgenic mouse neural regeneration
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LW-AFC,a new formula derived from Liuwei Dihuang decoction,ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune abnormalities in PrP-hAβPPswe/PS1^(ΔE9) transgenic mice
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作者 Jian-hui WANG Xi LEI +7 位作者 Xiao-rui CHENG Xiao-rui ZHANG Gang LIU Jun-ping CHENG Yi-ran XU Ju ZENG Wen-xia ZHOU Yong-xiang ZHANG 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2017年第10期1001-1001,共1页
OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mic... OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ) deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an Alpha LISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42 in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4^+CD25^+Foxp3^+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy. 展开更多
关键词 LW-AFC Alzheimer disease PrP-h AβPPswe/PS1ΔE9 transgenic mouse cognitive behavior amyloid-β neuron loss NEUROENDOCRINE lymphocyte subset cytokine
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Establishment of Human Interferon-Alpha Transgenic Mice Model
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作者 LI Wei-na YI Shuai +4 位作者 LIU Ye HU Rong-liang YUAN Bao REN Wen-zhi LIU Dian-feng 《Animal Husbandry and Feed Science》 CAS 2011年第2期18-20,24,共4页
[ Objective] To establish human interferon-alpha (hlFN-alpha) transgenic mice, which can be used to study antiviral activity of IFN-alpha in vivo. [Method] The expression vector was constructed by inserting the huma... [ Objective] To establish human interferon-alpha (hlFN-alpha) transgenic mice, which can be used to study antiviral activity of IFN-alpha in vivo. [Method] The expression vector was constructed by inserting the human IFN-alpha gene into a vector harboring human cytomegalovirus (CMV) promoter. The transgenic mice were created by the method of microinjection. The genotype of transgenic lines was identified by PCR and southern blotting. [ Result] Four lines of hlFN-alpha transgenic mice were established. Lymphocytes were collected from PCR-positive ,=1 generation mice and identified by RT-PCR, and mice of three lines were positive. ELISA and microplate dye-binding assay showed the expression of human IFN-alpha in the serum of mice which were positive in RT-PCR identification. [ Conclusion] The transgenic mice carrying CMV-controlled hlFN-alpha gene has been established successfully, which is essential for studying antiviral activity of IFN-alpha and genetic engineering breeding of disease-re- sistant animals. 展开更多
关键词 INTERFERON Transgenic mouse Cytomegalovirus promoter
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Critical thinking of Alzheimer's transgenic mouse model:current research and future perspective
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作者 Xinyue Li Meina Quan +4 位作者 Yiping Wei Wei Wang Lingzhi Xu Qi Wang Jianping Jia 《Science China(Life Sciences)》 SCIE CAS CSCD 2023年第12期2711-2754,共44页
Transgenic models are useful tools for studying the pathogenesis of and drug development for Alzheimer's Disease(AD).AD models are constructed usually using overexpression or knock-in of multiple pathogenic gene m... Transgenic models are useful tools for studying the pathogenesis of and drug development for Alzheimer's Disease(AD).AD models are constructed usually using overexpression or knock-in of multiple pathogenic gene mutations from familial AD.Each transgenic model has its unique behavioral and pathological features.This review summarizes the research progress of transgenic mouse models,and their progress in the unique mechanism of amyloid-βoligomers,including the first transgenic mouse model built in China based on a single gene mutation(PSEN1 V97L)found in Chinese familial AD.We further summarized the preclinical findings of drugs using the models,and their future application in exploring the upstream mechanisms and multi-target drug development in AD. 展开更多
关键词 Alzheimer's disease transgenic mouse model amyloid-βoligomers multi-target therapy
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A bacterial artificial chromosome transgenic mouse model for visualization of neurite growth 被引量:1
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作者 TAO Tao CHEN Chen +2 位作者 SUN Jie PENG YaJing ZHU MinSheng 《Science China(Life Sciences)》 SCIE CAS CSCD 2015年第4期373-378,共6页
Class Ⅲ β-tubulin (Tubb3) is a component of the microtubules in neurons and contributes to microtubule dynamics that are required for axon outgrowth and guidance during neuronal development. We here report a novel... Class Ⅲ β-tubulin (Tubb3) is a component of the microtubules in neurons and contributes to microtubule dynamics that are required for axon outgrowth and guidance during neuronal development. We here report a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses Class Ⅲ β-tubulin fused to mCherry, an improved monomeric red fluorescent protein, for the visualization of microtubules during neuronal development. A BAC containing Tubb3 gene was modified by insertion of mCherry complementary DNA downstream of Tubb3 coding sequence via homologous recombination, mCherry fusion protein was expressed in the nervous system and testis of the transgenic animal, and the fluorescent signal was observed in the neurons that located in the olfactory bulb, cerebral cortex, hippocampal formation, cerebellum, as well as the retina. Besides, Tubb3-mCherry fusion protein mainly distributed in neurites and colocalized with endogenous Class Ⅲ β-tubulin The fusion protein labels Purkinje cell dendrites during cerebellar circuit formation. Therefore, this transgenic line might be a novel tool for scientific community to study neuronal development both in vitro and in vivo. 展开更多
关键词 Tubb3 MCHERRY BAC transgenic mouse neuronal development Purkinje cells
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Understanding auditory neuropathy spectrum disorder: a system- atic review in transgenic mouse models 被引量:1
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作者 Li Wang Jing Guan +9 位作者 Hongyang Wang Lan Lan Qiujing Zhang Liang Zong Wan Du Wenping Xiong Fengjiao Li Kaiwen Wu Dayong Wang Qiuju Wang 《Science China(Life Sciences)》 SCIE CAS CSCD 2016年第5期480-486,共7页
Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mecha... Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mechanism underlying this disorder is not clear. We therefore performed a systematic review of genetic mouse models with different gene mutations to provide a valuable tool for better understanding of the process and the possible molecular mechanisms. Of the 18 articles retrieved, nine met the required criteria. All biochemical, histological, and electrophysiological results were recorded for each of the mouse models, as was the transgenic technology. This review provides a summary of different mouse models that may play an important role in the diagnosis and management of auditory neuropathy spectrum disorder in the future. 展开更多
关键词 auditory neuropathy spectrum disorder transgenic mouse models PATHOGENESIS systematic review
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