Production and analysis of transgenic mice exhibiting concentric hypertrophy in a heart using Cre-loxP system
使用 Cre-loxP 系统生产和分析心脏同心肥大的转基因小鼠
基本信息
- 批准号:11470165
- 负责人:
- 金额:$ 3.26万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Interleukin-1 (IL-1) is a physiologically active factor produced and secreted by a variety of cells including those responsible for controlling immunity, and it plays an important role in immunity reactions. IL-1 is known to inhibit contractility in isolated heart and myocytes, and also cause hypertrophy in cultured myocytes. All these findings came from the in vitro events, and therefore in vivo experiments using transgenic (Tg) mice are required In the past few years, we generated two lines overexpressing human IL-1α (hIL-1α) under control of CMV enhancer/chicken β-actin promoter (CAG) system, and found that of two lines one exhibited concentric hypertrophy with cardiomyocyte hypertrophy and died before sexual maturation (Isoda et al., J. Cardiac Failure 7, 355-364, 2001). Several analyses of this line revealed that the heart was composed by cells like proliferative fetal myocytes. This finding suggests that constitutively elevated levels of IL-1α in a heart may keep myocytes in a ju … More venile state even after birth. For further study, it was required for maintaining Tg mice expressing hIL-1α as those capable of producing offspring. For this purpose, we employed Cre-loxP system. We produced Tg mice carrying a CELIZ transgene comprising CAG promoter, loxP-floxed EGFP/CAT, hIL-1α cDNA, IRES and lacZ gene. We obtained two lines all of which appeared to express EGFP relatively strongly, as evaluated for the strength of EGFP fluorescence under UV illumination. When these Tg mice were mated to MNCE Tg mice (Sato et al., Mol Reprod Dev 60, 446-456, 2001) which expressed Cre gene ubiquitously, the resulting double Tg mice (aged 8-10 weeks) exhibited expression of hIL-1α and lacZ gene in various tissues including heart, but did not concentric hypertrophy in their hearts. This is probably due to extremely low level of hIL-1α produced in these double Tg mice, since Northern blot analysis failed to detect distinct band for hIL-1α mRNA. Further attempt to increase the level of hIL-1α is strictly required for manifestation of concentric hypertrophy in murine heart. Less
白细胞介素-1(Interleukin-1,IL-1)是由多种细胞包括负责控制免疫的细胞产生和分泌的生理活性因子,在免疫反应中起重要作用。已知IL-1抑制分离的心脏和肌细胞的收缩性,并且还引起培养的肌细胞的肥大。所有这些发现都来自体外事件,因此需要使用转基因(Tg)小鼠进行体内实验。在过去的几年中,我们在CMV增强子/鸡β-肌动蛋白启动子(CAG)系统的控制下产生了两个过表达人IL-1α(hIL-1α)的品系,并发现两个品系中的一个表现出同心性肥大伴心肌细胞肥大,并在性成熟前死亡(Isoda et al.,J. Cardiac Failure 7,355-364,2001)。对这条线的几项分析表明,心脏是由像增殖的胎儿肌细胞一样的细胞组成的。这一发现表明,心脏中IL-1α水平的组成性升高可能使心肌细胞处于一种应激状态, ...更多信息 甚至在出生后也是如此。为了进一步研究,需要维持表达hIL-1α的Tg小鼠作为能够产生后代的小鼠。为此,我们采用了Cre-loXP系统。我们产生了携带CELIZ转基因的Tg小鼠,所述CELIZ转基因包括CAG启动子、loxP-floxed EGFP/CAT、hIL-1α cDNA、IRES和lacZ基因。我们获得了两条线,所有这些似乎表达EGFP相对较强,在紫外线照射下的EGFP荧光强度的评价。当这些Tg小鼠与MNCE Tg小鼠交配时(Sato等人,Mol Reprod Dev 60,446-456,2001),所得到的双Tg小鼠(8-10周龄)在包括心脏在内的各种组织中表现出hIL-1α和lacZ基因的表达,但在它们的心脏中没有向心性肥大。这可能是由于这些双Tg小鼠产生的hIL-1α水平极低,因为北方印迹分析未能检测到hIL-1α mRNA的明显条带。进一步提高hIL-1α水平是小鼠心脏向心性肥大的表现。少
项目成果
期刊论文数量(40)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
M. Sato, Y. Yasuoka, H. Kodama, T. Watanabe, J. Miyazaki and M. Kimura: "New approach to cell lineage analysis in mammals using the Cre-loxP system"Molecular Reproduction and Development. 56. 34-44 (2000)
M. Sato、Y. Yasuoka、H. Kodama、T. Watanabe、J. Miyazaki 和 M. Kimura:“使用 Cre-loxP 系统进行哺乳动物细胞谱系分析的新方法”分子复制和发育。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
K.Isoda: "Myocardial hypertrophy in transgenic mice overexpressing human interleukin 1α"Journal of Cardiac Failure. 7. 355-364 (2001)
K.Isoda:“过度表达人白细胞介素 1α 的转基因小鼠的心肌肥大”《心力衰竭杂志》7. 355-364 (2001)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Niki Y, Yamada H, Seki S, Kikuchi T, Takahashi H, Toyama Y, Fijikawa K and Tada N: "Macrophage-and neutrophil-dominant arthritis in human IL-1α transgenic mice"Journal of Clinical Investigation. 107. 1127-1135 (2001)
Niki Y、Yamada H、Seki S、Kikuchi T、Takahashi H、Toyama Y、Fijikawa K 和 Tada N:“人 IL-1α 转基因小鼠中的巨噬细胞和中性粒细胞显性关节炎”临床研究杂志 107。1127-1135。 (2001)
- DOI:
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- 影响因子:0
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M. Sato, A. Ishikawa, A. Nagashima, T. Watanabe, N. Tada and M. Kimura: "Prolonged survival of mouse epididymal spermatozoa stored at room temperature"Genesis. 31. 147-155 (2001)
M. Sato、A. Ishikawa、A. Nagashima、T. Watanabe、N. Tada 和 M. Kimura:“室温下保存的小鼠附睾精子的长期存活”创世纪。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
M.Sato: "A New Approach to Cell Lineage Analysis in Mammals Using the Cre-loxP System"Molecular Repoduction and Development. (in press).
M.Sato:“使用 Cre-loxP 系统进行哺乳动物细胞谱系分析的新方法”分子复制和发育。
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- 影响因子:0
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SATO Masahiro其他文献
Stability of Contact Discontinuities in Electrostatic Hybrid- and Full-Vlasov Simulations
静电混合和全 Vlasov 模拟中接触不连续的稳定性
- DOI:
10.1585/pfr.15.1401002 - 发表时间:
2020 - 期刊:
- 影响因子:0.8
- 作者:
TSUJINE Naru;HARUKI Takayuki;UMEDA Takayuki;NARIYUKI Yasuhiro;SATO Masahiro - 通讯作者:
SATO Masahiro
Paradigm Shift in Program Structure of Particle-in-Cell Simulations
细胞内粒子模拟程序结构的范式转变
- DOI:
10.3233/apc200072 - 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
TSUJINE Naru;HARUKI Takayuki;UMEDA Takayuki;NARIYUKI Yasuhiro;SATO Masahiro;Umeda Takayuki - 通讯作者:
Umeda Takayuki
Evaluating higher moments in the transverse Kelvin?Helmholtz instability by full kinetic simulation
通过全动力学模拟评估横向开尔文?亥姆霍兹不稳定性中的更高矩
- DOI:
10.1063/1.5139442 - 发表时间:
2020 - 期刊:
- 影响因子:2.2
- 作者:
TSUJINE Naru;HARUKI Takayuki;UMEDA Takayuki;NARIYUKI Yasuhiro;SATO Masahiro;Umeda Takayuki;Umeda Takayuki - 通讯作者:
Umeda Takayuki
SATO Masahiro的其他文献
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{{ truncateString('SATO Masahiro', 18)}}的其他基金
Efficient enrichment of homozygous bi-allelic knockout microminiature porcine cells using a novel selection system and production of genome-edited cloned piglets
使用新型选择系统有效富集纯合双等位基因敲除微型猪细胞并生产基因组编辑的克隆仔猪
- 批准号:
15K07695 - 财政年份:2015
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Production of cloned genetically modified pigs by a new drug-free gene-modified cell isolation system
新型无药基因修饰细胞分离系统生产克隆转基因猪
- 批准号:
24580411 - 财政年份:2012
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of a general method for obtaining double KO swine cells which will be used as donors for production of cloned homozygous piglets
开发获得双 KO 猪细胞的通用方法,该细胞将用作生产克隆纯合仔猪的供体
- 批准号:
21580350 - 财政年份:2009
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Methods of characterizing magnetic multi-polar and spin-liquid phases
表征磁性多极和自旋液相的方法
- 批准号:
21740295 - 财政年份:2009
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Fundamental Investigation of Ultrasonic properties in Biological Tissues by Numerical Analysis.
通过数值分析对生物组织中的超声特性进行基础研究。
- 批准号:
06680869 - 财政年份:1994
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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HEART-SPECIFIC CREATINE KINASE REGULATORY ELEMENTS
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追踪心肌梗塞后心脏特异性免疫反应
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517001338 - 财政年份:
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Heisenberg Grants
Heart-specific antibodies as modulators of myocardial infarction (B06)
心脏特异性抗体作为心肌梗塞的调节剂 (B06)
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499097994 - 财政年份:
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Collaborative Research Centres