Glomerular-specific gene excision in vivo.
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.
Eremina
Vera
V
*The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada; and Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada.
Wong
Mark Andrew
MA
*The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada; and Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada.
Cui
Shiying
S
*The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada; and Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada.
Schwartz
Lois
L
*The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada; and Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada.
Quaggin
Susan E
SE
*The Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada; and Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada.
D000818:Animals; D004260:DNA Repair; D018390:Gene Targeting; D006801:Humans; D019426:Integrases / Q000235:genetics; D007678:Kidney Glomerulus / Q000166:cytology / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D011506:Proteins / Q000235:genetics; D019076:Transgenes / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics
D008565:Membrane Proteins; D011506:Proteins; D014764:Viral Proteins; C113267:nephrin; C045073:Cre recombinase; D019426:Integrases