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朱华,郭亚茜,杜晓鹏,李卓,秦川.无菌 APPswe / PS1ΔE9 双转基因小鼠模型建立及脑内斑块变化初步观察[J].中国实验动物学报,2019,27(4):521~526.
无菌 APPswe / PS1ΔE9 双转基因小鼠模型建立及脑内斑块变化初步观察
Establishment of germ free APPswe / PS1ΔE9 transgenic mice and changes of amyloid plaques in the brain
投稿时间:2019-02-26  
DOI:10. 3969 / j.issn.1005-4847. 2019. 04. 015
中文关键词:  转基因小鼠  无菌动物  剖宫产  淀粉样斑块
英文关键词:transgenic mice  germ-free mice  cesarean section  amyloid plaques  Alzheimer’s disease
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作者单位E-mail
朱华 卫健委人类疾病比较医学重点实验室,中国医学科学院医学实验动物研究所 北京协和医学院比较医学中心,北京 100021 zhuh@ cnilas.org 
郭亚茜 卫健委人类疾病比较医学重点实验室,中国医学科学院医学实验动物研究所 北京协和医学院比较医学中心,北京 100021  
杜晓鹏 卫健委人类疾病比较医学重点实验室,中国医学科学院医学实验动物研究所 北京协和医学院比较医学中心,北京 100021  
李卓 卫健委人类疾病比较医学重点实验室,中国医学科学院医学实验动物研究所 北京协和医学院比较医学中心,北京 100021  
秦川 卫健委人类疾病比较医学重点实验室,中国医学科学院医学实验动物研究所 北京协和医学院比较医学中心,北京 100021  
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中文摘要:
      目的 使用剖宫产净化方法建立无菌 APPswe / PS1ΔE9(PAP)双转基因小鼠模型并对动物脑内斑块沉积情况进行初步观察,为研究肠道菌群与阿尔茨海默症关系提供新的动物模型。方法 选择阳性PAP 雄性杂合子鼠与经产的C57 野生型雌鼠1∶2进行交配。怀孕母鼠在超净工作台内行剖宫产手术,用无菌ICR 小鼠代乳。术后每个月进行无菌状态检测;PCR 方法检测剖宫产所得PAP 仔鼠的基因型;免疫组化方法定量检测9 月龄PAP 小鼠脑内斑块变化情况。结果 实施剖宫产手术12 例,获仔鼠66 只,剖宫产存活率及离乳存活率分别为95. 45%(63/66)和95. 24% (60/63),净化后按国标检测无菌状态均为合格。免疫组化结果显示9 月龄无菌PAP 小鼠海马内斑块较同月龄SPF 级动物减少。结论 通过剖宫产净化技术去除了PAP 小鼠携带的菌群,9 月龄无菌PAP 小鼠脑内斑块减少。
英文摘要:
      Objective To establish a germ-free mouse strain to provide a new animal model for studies on therelationship between gut flora and Alzheimer’s disease and the changes of amyloid plaques in the brain, by establishing a APPswe / PS1ΔE9 (PAP) transgenic mouse model using a cesarean section decontamination technique. Methods Cesareansection was performed on pregnant PAP mice to obtain pups under a SPF barrier environment, and the pups were thentransferred to female germ-free ICR mice that served as foster mothers. Survival rates of the pups were calculated at 7 daysof age and after weaning. Pathogens were tested each month according to the national standards. The newborn PAP micewere genotyped by polymerase chain reaction (PCR). The deposition of Aβ plaques in brain tissue were observed usingimmunohistochemical staining. Result 12 cesarean sections were performed on pregnant PAP mice, and a total of 63 pupswere collected and transferred to a foster mother. The survival rate of pups after cesarean section and weaning was 95. 45%(63/66) and 95. 24% (60/63), respectively. Pathogens were tested after decontamination, and all the pups werepathogen-negative, thus met the requirement of germ-free mice. The deposition of Aβ plaques was lower in the germ-freePAP mice than in SPF mice of the same age. Conclusions A germ-free PAP mouse model is established by cesareansection and foster mother technique. This new animal model can be used for studies on the relationship between gut flora and Alzheimer’s disease and the changes of amyloid plaques in the brain tissue.
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