Functional Analysis of Collagen IV by Gene Targeting
通过基因打靶对 IV 型胶原蛋白进行功能分析
基本信息
- 批准号:09044308
- 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 international Scientific Research
- 财政年份:1997
- 资助国家:日本
- 起止时间:1997 至 1998
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Col4a6 null mice were created by introducing NeoィイD1RィエD1 gene into exon II of col4a6 gene. We analyzed if the gene is transcribed and translated into α6(IV) polypeptide by in site hybridization, Northern-blot hybridization, and immunohistochemical staining using α chain-specific monoclonal antibodies. The results demonstrated that the α6(IV) polypeptide was not stained at all in any tissues or organs in col4a6 null mice. We also analyzed if the mice have some phenotypes, but we have not detected ant differences between wild type and col4a6 null mice so far.We predicted the presence of the three molecular forms of type IV collagen ; [α1(IV)]2α2(IV), α3(IV)α4(IV)α5(IV), and [α5(IV)]2α6α(IV) by use of double staining of the monoclonal antibodies specific for α(IV) chains. The [α1(IV)]2α2(IV) form is present in all basement membranes, whereas the α3(IV)α4(IV)α5(IV) form is localized in glomeruler and alveolar basement membranes and the [α5(IV)]2α6(IV) form is in the Bowman's capsules of the kidney and dermal basement membrane regions. Heterogeneous distribution of the three molecular forms indicated that they may have specific roles in different basement membranes. To describe the biological roles of the molecules, we should think of how the three molecules are incorporated into the supramolecular aggregates of each basement membrane.We identified and characterized the breakpoint sequences of the deletion of DNA from a patient of diffuse leiomyomatosis associated with Alport syndrome. The results demonstrated that a deletion eliminates the first coding exon of COL4A5 and the first two of COL4A6. They also showed that the breakpoints share the same sequence, which is in turn closely homologous to the consensuses of topoisomerases I and II. Additional DNA evidence suggested that the male patient is a somatic for the mutation. This study is greatly relevant to the understanding of DL pathogenesis and its etiology.
将NeoィイD1RィエD1基因导入COL4a6基因外显子II,建立COL4a6缺失小鼠。我们通过原位杂交、Northern印迹杂交和免疫组织化学染色,利用α链特异性单抗分析了该基因是否转录并翻译成α6(IV)多肽。结果表明,α6(IV)多肽在Col4a6基因缺失小鼠的任何组织器官中均未见染色。我们还分析了小鼠是否具有某些表型,但到目前为止还没有检测到野生型和Col4a6缺失小鼠之间的差异。我们通过双重染色预测了三种IV型胶原的存在:[α1(IV)]2α2(IV),α3(IV)α4(IV)α5(IV)和[α5(IV)]2α6α(IV)。[α1(IV)]2α2(IV)存在于所有基底膜,α3(IV)α4(IV)α5(IV)存在于肾小球和肺泡基底膜,[α5(IV)]2α6(IV)存在于肾包膜和真皮基膜区域。这三种分子形式的异质性分布表明,它们可能在不同的基底膜中具有特定的作用。为了描述分子的生物学作用,我们应该考虑这三个分子是如何结合到每个基底膜的超分子聚集体中的。我们鉴定并表征了一例与Alport综合征相关的弥漫性子宫肌瘤病患者的DNA缺失的断点序列。结果表明,缺失可消除COL4A5的第一个编码外显子和COL4A6的前两个编码外显子。他们还显示,这些断裂点共享相同的序列,而这反过来又与拓扑异构酶I和II的共识密切相关。更多的DNA证据表明,这名男性患者是这种突变的体细胞。本研究对深入了解海绵状核变性的发病机制及其病因学具有重要意义。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Olson M.W.et al.: "High affinity binding of Matrix metalloproteinase-9 to the pro-α2(IV) chain of collagen IV. Role in binding of zymogen to the surface of human breast epthelial MCF10A cells." J.Biol.Chem.(in press). (1998)
Olson M.W. 等人:“基质金属蛋白酶-9 与 IV 型胶原蛋白的 pro-α2(IV) 链的高亲和力结合。酶原与人乳腺上皮 MCF10A 细胞表面结合的作用。J.Biol.Chem。” (出版中)。
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Khaleduzzaman M. et al: "Structure of the human type XIX collagen (COL19A1) gene that suggests it has arisen from an ancestor gene of the FACTT family"Genomics. 45. 304-312 (1997)
Khaleduzzaman M. 等人:“人类 XIX 型胶原蛋白 (COL19A1) 基因的结构表明它源自 FACTT 家族的祖先基因”基因组学。
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Sado Y. et al: "Induction of anti-GBM nephritis in rats by recombinant α3(IV) and α4(IV)NC1 of type IV collagen"Kidney International. 53. 664-671 (1998)
Sado Y.等人:“IV型胶原的重组α3(IV)和α4(IV)NC1诱导大鼠抗GBM肾炎”Kidney International 53. 664-671 (1998)。
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Ohnishi H, Oka T, Kusachi S, Nakanishi T, Takeda K, Nakahama M, Doi M, Murakami T, Ninomiya Y, Takigawa M, Tsuji T: "Increased expression of connective tissue growth factor in the infract zone of experimentally induced myocardial infraction in rats"J Mol
Ohnishi H、Oka T、Kusachi S、Nakanishi T、Takeda K、Nakahama M、Doi M、Murakami T、Ninomiya Y、Takikawa M、Tsuji T:“实验诱发的心肌梗死梗塞区结缔组织生长因子的表达增加
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Yoshikazu Sado, Ichiro Naito and Yoshifumi Ninomiya: "Glomerurler basement membrane and Goodpasture's syndrome"Clin. Exp. Nephrol. 2. 282-288 (1998)
Yoshikazu Sado、Ichiro Naito 和 Yoshifumi Ninomiya:“Glomerurler 基底膜和 Goodpasture 综合征”Clin。
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NINOMIYA Yoshifumi其他文献
NINOMIYA Yoshifumi的其他文献
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{{ truncateString('NINOMIYA Yoshifumi', 18)}}的其他基金
Anti tumor effect of micro RNA transferred by active targeting liposomes
主动靶向脂质体转移微小RNA的抗肿瘤作用
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Function of newly identified basal lamina structure fractone and regulation of neural stem cell differentiation at subventricular zone
新发现的基底层结构fractone的功能及其对室下区神经干细胞分化的调节
- 批准号:
16390048 - 财政年份:2004
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Function of subendothelial basement membranes in Blood-Brain Barrier
内皮下基底膜在血脑屏障中的功能
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14370434 - 财政年份:2002
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$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Functional Analysis of Basement Membrane Collagen Genes
基底膜胶原基因的功能分析
- 批准号:
11694280 - 财政年份:1999
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$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Inhibitory mechanism of vascular endothelial cell proliferation by endostatin
内皮抑素抑制血管内皮细胞增殖的机制
- 批准号:
11470274 - 财政年份:1999
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Reconstruction of basement membranes aiming at artificial organs
针对人工器官的基底膜重建
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10557113 - 财政年份:1998
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$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
Supramolecular Assembly and Function of New Basement Membrane Collagen Molecules
新型基底膜胶原分子的超分子组装及其功能
- 批准号:
08457154 - 财政年份:1996
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$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Biological function of basement membrane
基底膜的生物学功能
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07044268 - 财政年份:1995
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$ 3.26万 - 项目类别:
Grant-in-Aid for international Scientific Research
Biological Function of Type VIII Collagen
VIII 型胶原蛋白的生物学功能
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06044154 - 财政年份:1994
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$ 3.26万 - 项目类别:
Grant-in-Aid for international Scientific Research
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