Clinical and histopathological progression of lesions in lupus-prone (NZB x NZW) F1 mice

This study was conducted to review the progression with age of renal and other changes in (NZB x NZW) F-1 females obtained from a commercial colony, housed under SPF conditions. Sixty-two mice were given food and water ad libitum and sacrificed at intervals up to 47 weeks of age. Routine haernatology and urinalysis were performed at reaular intervals. The serum levels of IgA, IgG, IgM and antinuclear antibody levels were monitored along with urinary protein. Major organs and tissues from all animals were preserved and examined. Special attention was paid to the kidneys: in addition to routine 4-mum paraffin sections, 1-mum resin sections were prepared and examined. Positive levels of urinary protein (> 1 g/L) were only found in 50% of the animals, even at 32 weeks of age. Histopathologically, the expected type of glomerular damage was present; but the incidence and severity of the change were low, with only 33% of the mice affected at 32 weeks of age. Most mice had fatty vacuolation in the liver. At 24 weeks of age, 50% of the mice sacrificed had haemorrhagic degeneration of the liver. This was not seen at later time points. Only two mice survived until 47 weeks of age. In Summary, these findings were of the expected type, but at a much lower incidence and severity than formerly reported. The background of the strain and the experimental conditions are of great importance in the progress of these renal lesions. The lack of homogeneity of the renal changes would make it difficult to determine any influence of xenobiotics on the progress of autoimmune diseases. (C) 2004 Elsevier GmbH. All rights reserved.