ANTI-GBM GLOMERULONEPHRITIS IN MICE LACKING NITRIC-OXIDE SYNTHASE TYPE-2

Nitric oxide is synthesized in experimental immune complex glomerulone phritis due lu local induction of type 2 nitric oxide synthase (NOS2). To determine the role of NOS2, the course of accelerated anti-glomeru lar basement membrane glomerulonephritis (anti-GEM) was examined in mi ce homozygous for disruption of the NOS2 gene compared with heterozygo us littermates. Disease in the wild type strain (129Sv) was characteri zed by heavy albuminuria, glomerular neutrophil and macrophage infiltr ation and glomerular thrombosis. NOS2, interleukin 1B (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) mRNA Isere induced by 24 hours . The NOS2-deficient mutant mice and the heterozygous mice displayed e arly (24 hr) and full autologous phase (day 6) injury indistinguishabl e from the wild-type mice. The equivalent degree of albuminuria and gl omerular inflammation indicates that KOS2 does not play an essential r ole in this form of glomerulonephritis in the mouse.