酪氨酸激酶结合蛋白基因敲除小鼠不同脑区髓细胞2表达触发受体

Tongxiao Xu, Zhao-xia Wang, Yanxin Li, Kuo H. Yang, Wei Zhang, Wei Li, Yanlei Hao
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Yang, Wei Zhang, Wei Li, Yanlei Hao","doi":"10.3760/CMA.J.CN371468-20191025-00782","DOIUrl":null,"url":null,"abstract":"Objective \nTo compare the expression of myeloid cell trigger receptor expressed on myoid cell 2 (TREM2) in different brain regions of tyrosine kinase binding protein(TYROBP) knockout mice and wild-type mice at different months of age, and to explore the relationship between TREM2, TYROBP and early onset Alzheimer's disease(EOAD). \n \n \nMethods \nHealthy TYROBP gene knockout mice were divided into three groups according to the results of gene sequencing: the homozygous (TYROBP-/-) group, the heterozygous (TYROBP-/+ ) group, and the wild type (WT) group.Western blot and RT-qPCR were used to detect the expression of TREM2 in prefrontal cortex and hippocampus of 2, 4 and 6 month old mice in the three groups and with 10 in each group at each time point. \n \n \nResults \n(1) In the prefrontal cortex: Western blot and RT-qPCR results showed that compared with WT mice (2-month-old: (0.993±0.048), (1.654±0.033); 4-month-old: (0.503±0.019), (2.169±0.023); 6-month-old: (0.600±0.036), (1.468±0.057)), the levels of TREM2 protein and mRNA in 2-month-old TYROBP-/+ group ((0.746±0.062), (1.137±0.067)) and TYROBP-/- group ((0.661±0.028), (0.644±0.012)) were decreased.While in 4-month-old and 6-month-old TYROBP-/+ group (4-month-old: (1.140±0.006), (5.483±0.088); 6-month-old: (0.827±0.043), (3.020±0.082)) and TYROBP-/- group (4-month-old: (1.071±0.010), (3.012±0.150); 6-month-old: (0.627±0.026), (1.633±0.027)) were increased, especially in 4-month-old mice and the differences were statistically significant (F=12.946, 134.445; 725.318, 289.202; 12.172, 202.791; all P<0.05). (2) In the hippocampus: Western blot results showed that compared with WT mice (2-month-old: (1.268±0.036); 4-month-old: (0.813±0.010); 6-month-old: (0.312±0.021)), the level of TREM2 protein in 2-month-old TYROBP-/+ group ((0.804±0.034)) and TYROBP-/- group ((0.534±0.020)) were decreased.While in 4-month-old and 6-month-old TYROBP-/+ group ((0.932±0.011); (0.769±0.031)) and TYROBP-/- group ((0.910±0.014); (0.609±0.018)) were increased, especially in 4-month-old mice and the differences were statistically significant (F=142.807; 27.884; 94.067; all P<0.05). \n \n \nConclusion \nThe expression level of TREM2 decreases in 2-month-old TYROBP gene knockout mice while increases in 4-month-old and 6-month-old TYROBP gene knockout mice.It is presumed that TREM2/TYROBP signal pathway participates in the pathological process of EOAD and plays different roles in different pathological stages of EOAD. \n \n \nKey words: \nTyrosine kinase binding protein; Triggering receptor expressed on myeloid cell 2; Alzheimer's disease; Mice","PeriodicalId":9940,"journal":{"name":"中华行为医学与脑科学杂志","volume":"29 1","pages":"102-108"},"PeriodicalIF":0.0000,"publicationDate":"2020-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Expressions of triggering receptor expressed on myeloid cell 2 in different brain regions in tyrosine kinase binding protein gene knockout mice\",\"authors\":\"Tongxiao Xu, Zhao-xia Wang, Yanxin Li, Kuo H. 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(2) In the hippocampus: Western blot results showed that compared with WT mice (2-month-old: (1.268±0.036); 4-month-old: (0.813±0.010); 6-month-old: (0.312±0.021)), the level of TREM2 protein in 2-month-old TYROBP-/+ group ((0.804±0.034)) and TYROBP-/- group ((0.534±0.020)) were decreased.While in 4-month-old and 6-month-old TYROBP-/+ group ((0.932±0.011); (0.769±0.031)) and TYROBP-/- group ((0.910±0.014); (0.609±0.018)) were increased, especially in 4-month-old mice and the differences were statistically significant (F=142.807; 27.884; 94.067; all P<0.05). \\n \\n \\nConclusion \\nThe expression level of TREM2 decreases in 2-month-old TYROBP gene knockout mice while increases in 4-month-old and 6-month-old TYROBP gene knockout mice.It is presumed that TREM2/TYROBP signal pathway participates in the pathological process of EOAD and plays different roles in different pathological stages of EOAD. \\n \\n \\nKey words: \\nTyrosine kinase binding protein; Triggering receptor expressed on myeloid cell 2; Alzheimer's disease; Mice\",\"PeriodicalId\":9940,\"journal\":{\"name\":\"中华行为医学与脑科学杂志\",\"volume\":\"29 1\",\"pages\":\"102-108\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-02-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中华行为医学与脑科学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3760/CMA.J.CN371468-20191025-00782\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中华行为医学与脑科学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3760/CMA.J.CN371468-20191025-00782","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

目的比较酪氨酸激酶结合蛋白(TYROBP)敲除小鼠和不同月龄野生型小鼠不同脑区肌样细胞2(TREM2)上表达的髓细胞触发受体的表达,探讨TREM2、TYROBP与早发性阿尔茨海默病(EOAD)的关系。方法根据基因测序结果将健康的TYROBP基因敲除小鼠分为三组:纯合型(TYROBP-/-)组、杂合型(TYROBP-/+)组和野生型(WT)组。采用Western blot和RT-qPCR检测三组2、4和6月龄小鼠前额叶皮层和海马TREM2的表达,每组10只。结果(1)前额叶皮层:Western blot和RT-qPCR结果显示,与WT小鼠(2月龄:(0.993±0.048),(1.654±0.033)相比;4月龄:(0.503±0.019),(2.169±0.023);6个月龄:(0.600±0.036),(1.468±0.057),2个月龄TYROBP-/+组(0.746±0.062),(1.137±0.067)和TYROBP/-组(0.661±0.028),(0.644±0.012)TREM2蛋白和mRNA水平降低。而在4个月大和6个月大的TYROBP-/+组(4个月龄:(1.140±0.006),(5.483±0.088);6个月龄:(0.827±0.043),(3.020±0.082))和TYROBP-/-组(4个月龄,(1.071±0.010),(3.0 12±0.150);6个月大:(0.627±0.026),(1.633±0.027))增加,特别是在4个月大的小鼠中,差异具有统计学意义(F=12.94613.445;725.318289.202;12.17202.791;均P<0.05);4月龄:(0.813±0.010);6月龄:(0.312±0.021)),2月龄TYROBP-/+组(0.804±0.034)和TYROBP/-组(0.534±0.020)TREM2蛋白水平下降。而在4个月大和6个月大的TYROBP-/+组((0.932±0.011);(0.769±0.031))和TYROAP-/-组(0.910±0.014);(0.609±0.018))表达增加,尤其是在4月龄小鼠中,差异有统计学意义(F=142.807;27.884;94.067;均P<0.05)。TREM2/TYROBP信号通路参与EOAD的病理过程,在EOAD的不同病理阶段发挥不同的作用。关键词:酪氨酸激酶结合蛋白;骨髓细胞2上表达的触发受体;阿尔茨海默病;老鼠
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Expressions of triggering receptor expressed on myeloid cell 2 in different brain regions in tyrosine kinase binding protein gene knockout mice
Objective To compare the expression of myeloid cell trigger receptor expressed on myoid cell 2 (TREM2) in different brain regions of tyrosine kinase binding protein(TYROBP) knockout mice and wild-type mice at different months of age, and to explore the relationship between TREM2, TYROBP and early onset Alzheimer's disease(EOAD). Methods Healthy TYROBP gene knockout mice were divided into three groups according to the results of gene sequencing: the homozygous (TYROBP-/-) group, the heterozygous (TYROBP-/+ ) group, and the wild type (WT) group.Western blot and RT-qPCR were used to detect the expression of TREM2 in prefrontal cortex and hippocampus of 2, 4 and 6 month old mice in the three groups and with 10 in each group at each time point. Results (1) In the prefrontal cortex: Western blot and RT-qPCR results showed that compared with WT mice (2-month-old: (0.993±0.048), (1.654±0.033); 4-month-old: (0.503±0.019), (2.169±0.023); 6-month-old: (0.600±0.036), (1.468±0.057)), the levels of TREM2 protein and mRNA in 2-month-old TYROBP-/+ group ((0.746±0.062), (1.137±0.067)) and TYROBP-/- group ((0.661±0.028), (0.644±0.012)) were decreased.While in 4-month-old and 6-month-old TYROBP-/+ group (4-month-old: (1.140±0.006), (5.483±0.088); 6-month-old: (0.827±0.043), (3.020±0.082)) and TYROBP-/- group (4-month-old: (1.071±0.010), (3.012±0.150); 6-month-old: (0.627±0.026), (1.633±0.027)) were increased, especially in 4-month-old mice and the differences were statistically significant (F=12.946, 134.445; 725.318, 289.202; 12.172, 202.791; all P<0.05). (2) In the hippocampus: Western blot results showed that compared with WT mice (2-month-old: (1.268±0.036); 4-month-old: (0.813±0.010); 6-month-old: (0.312±0.021)), the level of TREM2 protein in 2-month-old TYROBP-/+ group ((0.804±0.034)) and TYROBP-/- group ((0.534±0.020)) were decreased.While in 4-month-old and 6-month-old TYROBP-/+ group ((0.932±0.011); (0.769±0.031)) and TYROBP-/- group ((0.910±0.014); (0.609±0.018)) were increased, especially in 4-month-old mice and the differences were statistically significant (F=142.807; 27.884; 94.067; all P<0.05). Conclusion The expression level of TREM2 decreases in 2-month-old TYROBP gene knockout mice while increases in 4-month-old and 6-month-old TYROBP gene knockout mice.It is presumed that TREM2/TYROBP signal pathway participates in the pathological process of EOAD and plays different roles in different pathological stages of EOAD. Key words: Tyrosine kinase binding protein; Triggering receptor expressed on myeloid cell 2; Alzheimer's disease; Mice
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期刊介绍: "Chinese Journal of Behavioral Medicine and Brain Science" (CN 37-1468/R, ISSN 1674-6554) is a national academic journal under the supervision of the National Health Commission, sponsored by the Chinese Medical Association and Jining Medical College. The journal was founded in June 1992 and was formerly known as "Chinese Journal of Behavioral Medicine" (1992-1993) and "Chinese Behavioral Medical Science" (1994-2008). In 2009, it was renamed "Chinese Journal of Behavioral Medicine and Brain Science" with the approval of the State Administration of Press, Publication, Radio, Film and Television. The purpose of "Chinese Journal of Behavioral Medicine and Brain Science" is to implement the health and health policies of the Party and the State, implement the principle of combining theory with practice and popularization and improvement, and reflect the major progress in the theory and practical application of behavioral medicine and brain science in my country. It publishes academic papers and scientific research results in the field of behavioral medicine and brain science in my country, and has columns such as monographs/reviews, basic research, clinical research, health prevention, methods and techniques, psychological behavior and evaluation, and systematic evaluation.
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