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
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
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.
1) Ogura et al. Lab Anim 23:169-174 (1989),
2) Ogura et al. Virchows Archiv A 417:223-228 (1990)
Department of Anatomy, Sapporo Medical University Schoool of Medicine