In mice, proteinuria and renal inflammatory responses to albumin overload are strain-dependent.
BACKGROUND
The availability of genetically modified mice has increased the need for relevant mouse models of renal disease, but widely used C57BL/6 mice often show resistance to proteinuria. 129/Sv mice are considered more sensitive to certain renal models. Albumin overload, an important model of proteinuric disease, induces marked proteinuria in rats but barely in C57BL/6 mice. We hypothesized that albumin overload would induce more proteinuria in 129S2/Sv than C57BL/6J mice.


METHODS
Male and female C57BL/6J and 129S2/Sv mice received bovine serum albumin (BSA) for 11 days. Control groups received saline injections. Injected BSA was immunohistochemically localized to study intrarenal handling of overloaded protein. Renal macrophage infiltration (F4/80 immuno-staining) and glomerular ultrastructure (electron microscopy) were assessed.


RESULTS
The BSA-treated groups were similarly hyperproteinemic at Day 11 (D11). Proteinuria differed widely. In C57BL/6J mice, it remained unchanged in females but significantly, though mildly, increased in males (from 3+/-1 to 8+/-2 mg/day, P < 0.05). In 129S2/Sv, proteinuria was marked in both males and females (4+/-1 to 59+/-14, and 0.6+/-0.2 to 29+/-9 mg/day, respectively, both P < 0.01). Proteinuria was accompanied by tubulo-interstitial macrophage infiltration in 129S2/Sv mice. Injected BSA was visualized within glomeruli in both strains and in the urinary space and tubules of 129S2/Sv but not C57BL/6J mice, indicating much greater glomerular leakage in the former. No glomerular macrophages or ultra-structural differences were detected.


CONCLUSIONS
There are major strain differences in the proteinuria and renal inflammatory response of mice to albumin overload, which are not due to structural variation in the filtration barrier but possibly to functional differences in glomerular protein permeability.
Ishola
David A
DA
Department of Nephrology, University Medical Center, Utrecht, The Netherlands.
van der Giezen
Dionne M
DM
Hahnel
Brunhilde
B
Goldschmeding
Roel
R
Kriz
Wilhelm
W
Koomans
Hein A
HA
Joles
Jaap A
JA
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007267:Injections; D007678:Kidney Glomerulus / Q000648:ultrastructure; D007684:Kidney Tubules / Q000648:ultrastructure; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D012709:Serum Albumin / Q000008:administration & dosage / Q000633:toxicity; D012737:Sex Factors
D012709:Serum Albumin