Glomerular-specific gene excision in vivo.

Glomerular-specific gene excision in vivo.
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体内肾小球特异性基因切除。

DOI:
--
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发表时间:
2002
影响因子:
13.6
通讯作者:
S. Quaggin
S. Quaggin
中科院分区:
医学1区
文献类型:
--
作者:
V. Eremina;M. Wong;S. Cui;L. Schwartz;S. Quaggin

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足细胞(肾小球内脏上皮细胞)是在肾小球中发现的高度特化的细胞,构成血液和泌尿空间之间的过滤屏障的主要部分。最近,鉴定了许多与常染色体显性和隐性形式的人类肾病综合征相关的基因,这使得我们能够深入了解许多与足细胞独特特征(例如裂隙隔膜)相关的分子。尽管我们对足细胞生物学的理解取得了这些重大进展,但足细胞中表达的许多基因的功能仍然未知。在小鼠胚胎干细胞(ES细胞)中使用同源重组进行靶向基因破坏是确定体内基因生物学功能的有力工具。然而,由此产生的胚胎致死或多效性表型通常妨碍对特定肾细胞类型中的基因进行分析。为了克服这个问题,在 Nphs1(去氧肾上腺素)启动子(Neph-Cre)的控制下,产生了肾小球特异性 Cre 重组酶转基因鼠系。本文报道了 Cre 介导的成功切除体内足细胞中的“floxed”转基因。该小鼠始祖系代表了操纵足细胞基因表达的强大新工具,并将为整个动物的足细胞生物学提供有价值的见解。
Podocytes (glomerular visceral epithelial cells) are highly specialized cells that are found in the renal glomerulus and make up a major portion of the filtration barrier between the blood and urinary spaces. Recently, the identification of a number of genes responsible for both autosomal dominant and recessive forms of human nephrotic syndrome has provided insight into a number of molecules responsible for unique features of the podocyte such as the slit diaphragms. Despite these major advances in our understanding of podocyte biology, the function of many genes expressed in the podocyte remains unknown. Targeted gene disruption using homologous recombination in murine embryonic stem cells (ES cells) is a powerful tool to determine the biologic function of genes in vivo. However, resulting embryonic lethal or pleiotropic phenotypes often preclude the analysis of genes in specific renal cell types. To overcome this problem, a glomerular-specific Cre-recombinase transgenic murine line under the control of the Nphs1 (nephrin) promoter (Neph-Cre) was generated. This article reports successful Cre-mediated excision of a 'floxed' transgene specifically in podocytes in vivo. This murine founder line represents a powerful new tool for the manipulation of the expression of genes in podocytes and will provide valuable insight into podocyte biology in the whole animal.
DOI: 10.1152/ajprenal.2000.279.2.f275
发表时间: 2000-08-01
影响因子: 4.2
作者:
Robert, B;Zhao, XM;Abrahamson, DR
通讯作者: Abrahamson, DR
DOI: 10.1172/jci119163
发表时间: 1997-01-15
影响因子: 15.9
作者:
Pagtalunan, ME;Miller, PL;Meyer, TW
通讯作者: Meyer, TW
DOI: 10.1073/pnas.85.22.8668
发表时间: 1988-11-01
影响因子: 11.1
作者:
COLBEREGARAPIN, F;CHRISTODOULOU, C;CANDREA, A
通讯作者: CANDREA, A
发育中的肾脏中的肾小球发生。
DOI: --
发表时间: 1991
影响因子: 3.3
作者:
Abrahamson,DR
通讯作者: Abrahamson,DR
有证据表明表达 flk-1 的胚胎肾细胞是内在的血管生成血管细胞。
DOI: 10.1152/ajprenal.1996.271.3.f744
发表时间: 1996
期刊: The American journal of physiology.
影响因子: --
作者:
Robert,B;StJohn,PL;Hyink,DP;Abrahamson,DR
通讯作者: Abrahamson,DR