Eremina Vera, Wong Mark Andrew, Cui Shiying, Schwartz Lois, Quaggin Susan E
*The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada; and Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada.
J Am Soc Nephrol. 2002 Mar;13(3):788-793. doi: 10.1681/ASN.V133788.
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.
足细胞（肾小球脏层上皮细胞）是高度特化的细胞，位于肾小体中，构成血液与尿液腔隙之间滤过屏障的主要部分。最近，对一些导致常染色体显性和隐性人类肾病综合征的基因的鉴定，使我们对一些负责足细胞独特特征（如裂孔隔膜）的分子有了深入了解。尽管我们对足细胞生物学的理解取得了这些重大进展，但足细胞中许多基因的功能仍然未知。利用小鼠胚胎干细胞（ES细胞）中的同源重组进行靶向基因敲除，是一种在体内确定基因生物学功能的强大工具。然而，由此产生的胚胎致死或多效性表型往往妨碍对特定肾细胞类型中基因的分析。为了克服这个问题，构建了一种在Nphs1（nephrin）启动子（Neph-Cre）控制下的肾小球特异性Cre重组酶转基因小鼠品系。本文报道了在体内成功通过Cre介导特异性地在足细胞中切除“floxed”转基因。这个小鼠始祖品系是一种用于操纵足细胞中基因表达的强大新工具，将为整个动物体内的足细胞生物学提供有价值的见解。
