WT1 Activates a Glomerular-Specific Enhancer Identified from the Human Nephrin Gene

G. Guo
2004 Journal of the American Society of Nephrology  
The glomerular filtration barrier separates the blood from the urinary space. Nephrin is a transmembrane protein that belongs to the immunoglobulin superfamily and is localized to the slit diaphragms that are a critical component of this filtration barrier. Mutations in the nephrin gene (NPHS1) lead to congenital Finnish nephropathy, whereas alterations in the level of nephrin expression have been identified in a wide range of acquired glomerular diseases. A 186-bp fragment from the human NPHS1
more » ... promoter is capable of directing podocyte-specific expression of a ␤-galactosidase transgene when placed in front of a heterologous minimal promoter in transgenic mice. The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner. Taken together, these results suggest that WT1 may be required for regulation of the NPHS1 gene in vivo.
doi:10.1097/01.asn.0000143474.91362.c4 pmid:15504938 fatcat:zlapqkmi7rhfthxemy7ilngjh4