Complementation of juxtaglomerular cell granulation in Ren‐ 1d null mice by human renin

Abstract

Mice null for the Ren‐1d gene lack renin storage granules in their juxtaglomerular cells and exhibit altered macula densa morphology. Three lines of transgenic mice carrying a 55kbp transgene encompassing the human renin (hRen) locus were generated and crossed onto a Ren1d‐null background. Expression of hRen was seen to restore granulation in juxtaglomerular (JG) cells in a transgene expression level‐dependent manner, suggesting that a threshold level of renin expression is required for the formation of dense renin‐containing granules. Complementation of the phenotype by the human enzyme suggests that hRen and mouse Ren1d share conserved epitopes required for trafficking renin into the regulated secretion pathway and hence for granulopoiesis. To dissect the granulation phenotype in detail, 2D electron microscopic (EM) images were taken of kidney sections, which were then reconstructed in 3D to show the full extent of renin granular structure. As expected, the expression of hRen, which does not effectively cleave mouse angiotensinogen, was unable to restore macula densa morphology, indicating that a locally active RAS is required for normal macular densa structure and function.