Adriamycin nephropathy in severe combined immunodeficient (SCID) mice

Abstract

Experimental focal glomerulosclerosis is a model of chronic proteinuric renal disease that has been induced in both rats and mice. In mice, the adriamycin (ADR)induced nephropathy model is a robust experimental analogue of human focal glomerulosclerosis [1]. Renal injury in the ADR-induced nephropathy model is characterized by changes in both the tubulointerstitial and glomerular compartments. Within the interstitium, there is an increase in interstitial volume, tubular atrophy, collagen deposition and increased numbers of CD4þ T cells, CD8þ T cells and macrophages [1]. In mice with established adriamycin nephropathy, depletion of CD4þ T lymphocytes worsens glomerular and interstitial injury [2] whilst depletion of CD8þ T lymphocytes ameliorates disease [3]. Therefore, lymphocytes play a pivotal role in renal injury in adriamycin nephropathy (AN). The tubulointerstitium also contains other inflammatory cells such as macrophages, dendritic cells and NK cells. Using lymphocyte-deplete animals enables study of the individual contribution of these cell populations to renal injury. SCID (severe combined immunodeficient) mice are homozygous for an autosomal recessive mutation that leads to the absence of lymphocytes and hypogammaglobulinaemia [4], and are found in BALB/c mice. Adriamycin nephropathy can be induced in immunocompetent BALB/c mice [1]. Previous studies in our laboratory have shown that NK cells do not play a significant role in this model [5]. The aim of the present study was to determine if the model of AN could be established in SCID mice. We found that tail-vein injection of adriamycin induces a stable and reproducible model of proteinuric renal disease in lymphocyte-deplete BALB/c mice at half the dose required for immunocompetent BALB/c mice.