Three-Dimensional Reconstruction of the Mouse Nephron

Abstract

Renal function is crucially dependent on renal microstructure which provides the basis for the regulatory mechanisms that control the transport of water and solutes between filtrate and plasma and the urinary concentration. This study provides new, detailed information on mouse renal architecture, including the spatial course of the tubules, lengths of different segments of nephrons, histotopography of tubules and vascular bundles, and epithelial ultrastructure at well-defined positions along Henle's loop and the distal convolution of nephrons. Three-dimensional reconstruction of 200 nephrons and collecting ducts was performed on aligned digital images, obtained from 2.5-m-thick serial sections of mouse kidneys. Important new findings were highlighted: (1) A tortuous course of the descending thin limbs of long-looped nephrons and a winding course of the thick ascending limbs of short-looped nephrons contributed to a 27% average increase in the lengths of the corresponding segments, (2) the thick-walled tubules incorporated in the central part of the vascular bundles in the inner stripe of the outer medulla were identified as thick ascending limbs of long-looped nephrons, and (3) three types of short-looped nephron bends were identified to relate to the length and the position of the nephron and its corresponding glomerulus. The ultrastructure of the tubule segments was identified and suggests important implications for renal transport mechanisms that should be considered when evaluating the segmental distribution of water and solute transporters within the normal and diseased kidney. T he renal architecture is arranged elaborately to fulfill the physiologic demands for reabsorption of filtered substances and for urine concentration. The architecture includes the formation of the renal zones, the population of short-looped nephrons (SLN) and long-looped nephrons (LLN), the distribution of the tubule segments of nephrons, the tubular-vascular histotopography in medulla, and the epithelial configurations of the different tubule segments.From the 1960s to the 1980s, Kriz and others studied the renal microstructure, including the distribution of nephrons, the tubular-vascular relations in the medullary zones, and the ultrastructure of the epithelia along Henle's loop. Simultaneously, the diversities in renal structure were demonstrated between different species, including rat, mouse, hamster, and rabbit (1-3). In the late 1980s, a standard nomenclature for the kidney structure, which has been widely adopted, was published (4). With the development of digital techniques, three-dimensional (3D) representations of the tubule segments of nephrons were performed to a limited extent at the proximal tubules (PT) (5), distal tubule (6), and at the thin limbs (TL) of the LLN in the inner medulla (IM) (7) of rats. Two mathematical regionalbased models combining morphologic and immunohistochemical findings have been set up to simulate the urine concentration mechanism in rat medulla (8).At present, a large body of basic nephrol...

Urine-Concentrating Mechanism in the Inner Medulla

“…We used the rat kidney in our work because of the enormous amount of physiologic data, including data on the concentrating mechanism, available for this species. However, our preliminary work and studies by others (44,45) suggest that the three-dimensional relationships in the mouse renal medulla are similar to those in the rat. Our preliminary studies also indicate that rodent and human inner medullary architecture share fundamental similarities.…”

Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria

“…2G), and anti-CLCK1 (Fig. 2K) antibodies (41,43,50,55,58,78,79). These staining patterns indicate that CBS (and CTH) is predominantly expressed in the proximal convoluted tubules (PCT) and proximal straight tubules (PST).…”

Urea and Renal Function in the 21st Century

“…Recycling first was demonstrated by Lassiter et al (55), who showed that the mass flow rate of urea in the superficial tubule exceeds the filtered load of urea. It has been proposed (54) that a major element of urea secretion into Henle's loop is via transfer from the vasa recta to the thin descending limbs of short-loop nephrons in the vascular bundles of the outer medulla, where these two structures are in close apposition (56,57). The chief urea transporter of the vasa recta is UT-B, whereas the chief urea transporter in the thin descending limbs is UT-A2 ( Figures 1 and 3).…”