Spontaneous Nephrotic (ICGN) Mice

Haruyuki TATSUMI, Shoji SATOH, Munehiro OKAMOTO, Toshihiko ASANO*, Tsutomu KUROSAWA** and Masahiro NAKAMURA*

 
      *Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan
   **Institute of Experimental Animal Sciences, Osaka University Medical School, Osaka, Japan
***Department of Veterinary Science, National Institute of Health, Tokyo, Japan

Introduction:

Spontaneous nephrotic mice (ICGN mice), a mutant strain of mouse from outbred ICR, develop proteinuria, hypoproteinemia and hypercholesterolaemia.

ICGN mouse (two months old), showing highly developed edema.

These clinical symptoms are steadily progressive, and finally followed by chronic renal failure. Therefore, ICGN is expected to be a useful model for human nephrotic syndrome or chronic renal failure.

Morphological Features:

As reported previously (1,2), the histopathological findings are; a marked thickening of the glomerular capillary basement membrane, an increase of mesangial matrix without cellular proliferation, stenosis or occlusion of glomerular capillaries and fusion of podocyte foot processes. Besides the glomerular lesions, we investigated the details of the changes of the renal tubules in the late stage (5-10 months old) by light and electron microscopy. All renal tubules were not equally compromised, and some of them seemed to be normal. The renal cortex of the ICGN mice became thinner than that of the control ICR mice. Juxtamedullary glomeruli were hardly seen, whereas highly dilated renal tubules were found in the juxtamedullary cortex. Some of the dilated renal tubules contained urinary casts, while others did not. In the transitional area between the juxtamedullary cortex and medulla, moderately dilated renal tubules were observed, but the diameter of the renal tubule in the medulla was not so different from that of the control mice. In the cortex, a great increase of the thickness of the basal lamina was also seen around renal tubules that had narrow and sometimes completely occluded lumen. This thick basal lamina had an increased level of PAS-positive amorphous substances. Renal tubules with occluded lumen were mainly observed adjacent to the severely affected glomeruli. On the other hand, the basal lamina around the dilated renal tubules seemed to be normal in thickness, and the tubular cells were very flat in shape with poorly developed microvilli. PAS-reaction was much decreased in the microvilli of the proximal tubules. To determine the precise locations of the affected renal tubules and the proportion of affected nephrons, three-dimensional studies are required.