title: Inducible gene silencing in podocytes: a new tool for studying glomerular function.
abstract: Glomerular filtration is one of the primary functions of the kidney. Podocytes, a highly specialized cell type found in glomeruli, are believed to play a critical role in that function. Null mutations of genes expressed in podocytes like WT1, nephrin, and NEPH1 result in an embryo and perinatal lethal phenotype and therefore do not allow the functional analysis of these genes in the adult kidney. Here is describes the generation of a model that will allow such studies. We have engineered transgenic mice in which the disruption of targeted genes can be induced in a temporally controlled fashion in podocytes. For this, a transgene encoding the mutated estrogen receptor-Cre recombinase fusion protein was introduced into the mouse genome. Animals were crossed with Z/AP reporter mice to test for efficient and inducible recombination. We found that, after injection of inducer drug tamoxifen, Cre fusion protein translocates to the nuclei of podocytes, where it becomes active and mediates recombination of DNA carrying loxP target sequences. These animals provide for the first time a tool for silencing genes selectively in podocytes of adult animals.
authors.affiliation: Section of Immunology & Infection and CMMI, Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College London, UK. l.bugeon@ic.ac.uk
authors.forename: Laurence
authors.initials: L
authors.lastname: Bugeon
authors.forename: Aliki
authors.initials: A
authors.lastname: Danou
authors.forename: David
authors.initials: D
authors.lastname: Carpentier
authors.forename: Paul
authors.initials: P
authors.lastname: Langridge
authors.forename: Nelofer
authors.initials: N
authors.lastname: Syed
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Dallman
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D020868:Gene Silencing; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007674:Kidney Diseases / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010641:Phenotype; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D025721:WT1 Proteins; C045073:Cre recombinase; D019426:Integrases