Pod1 is required in stromal cells for glomerulogenesis.

Pod1 (capsulin/epicardin/Tcf21) is a basic-helix-loop-helix transcription factor that is highly expressed in the mesenchyme of developing organs that include the kidney, lung, gut, and heart. Null Pod1 mice are born but die shortly after birth due to a lack of alveoli in the lungs and cardiac defects. In addition, the kidneys are hypoplastic and demonstrate disrupted branching morphogenesis of the ureteric bud epithelium, a marked reduction in the number of nephrons, a delay in glomerulogenesis, and blood vessel abnormalities. To further dissect the cellular function of Pod1 during kidney development, chimeric mice were generated through aggregations of null Pod1 embryonic stem cells and murine embryos ubiquitously expressing enhanced green fluorescent protein (GFP). Histologic, immunohistochemical, and in situ hybridization analysis of the resulting chimeric offspring demonstrated both cell autonomous and non-cell autonomous roles for Pod1 in the differentiation of specific renal cell lineages that include peritubular interstitial cells and pericytes. Most strikingly, the glomerulogenesis defect was rescued by the presence of wild-type stromal cells, suggesting a non-cell autonomous role for Pod1 in this cell population.

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.