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J Am Soc Nephrol 13:788-793, 2002
© 2002 American Society of Nephrology


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Glomerular-Specific Gene Excision In Vivo

Vera Eremina*, Mark Andrew Wong*, Shiying Cui*, Lois Schwartz* and Susan E. Quaggin*{dagger}

*The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada; and {dagger}Division of Nephrology, St. Michael’s Hospital, Toronto, Ontario, Canada.

Correspondence to: Susan E. Quaggin, The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5. Phone: 416-586-4800; Fax: 416-586-8588; Email: quaggin{at}mshri.on.ca

Abstract

ABSTRACT. 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.




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