The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation of glomerular visceral epithelial cells

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Abstract

Molecular components of the glomerular filtration mechanism play critical roles in renal diseases. Many of these components are produced during the final stages of differentiation of glomerular visceral epithelial cells, also known as podocytes. While basic domain leucine zipper (bZip) transcription factors of the Maf subfamily have been implicated in cellular differentiation processes, Kreisler (Krml1/MafB), the gene affected in the mouse kreisler (kr) mutation, is known for its role in hindbrain patterning. Here we show that mice homozygous for the krenu mutation develop renal disease and that Kreisler is essential for cellular differentiation of podocytes. Consistent with abnormal podocyte differentiation, krenu homozygotes show proteinuria, and fusion and effacement of podocyte foot processes, which are also observed in the nephrotic syndrome. Kreisler acts during the final stages of glomerular development - the transition between the capillary loop and mature stages - and downstream of the Pod1 basic domain helix-loop-helix transcription factor. The levels of Podocin, the gene mutated in autosomal recessive steroid-resistant nephrotic syndrome (NPHS2), and Nephrin, the gene mutated in congenital nephrotic syndrome of the Finnish type (NPHS1), are slightly reduced in krenu/krenu podocytes. However, these observations alone are unlikely to account for the aberrant podocyte foot process formation. Thus, Kreisler must regulate other unknown genes required for podocyte function and with possible roles in kidney disease. © 2002 Elsevier Science (USA).

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Sadl, V. S., Jin, F., Yu, J., Cui, S., Holmyard, D., Quaggin, S. E., … Cordes, S. P. (2002). The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation of glomerular visceral epithelial cells. Developmental Biology, 249(1), 16–29. https://doi.org/10.1006/dbio.2002.0751

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