Glomerulonephritis with fibrillary deposition in a transgenic mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse)

Glomerulonephritis was observed in a 34-week-old transgenic CB6F(1) mouse c arrying the human prototype c-Ha-ras gene (rasH2 mouse) from a medium term carcinogenicity study of N-methyl-M-nitrosourea (MNU). Lesions were charact erized by severe diffuse enlargement and prominent hyalinization of glomeru li. The hyaline material was positive for pel iodic acid-Schiff but negativ e for amyloid by the Congo red method. Immunohistochemically, affected glom eruli were positive for polyclonal anti-mouse IgG. Ultrastructurally, there were characteristic subendothelial and mesangial deposits composed of fibr ils showing a fingerprint pattern. Lamellae were 7.5-14.3 nm in diameter an d formed multilayered structures. Ln addition to the renal lesions, a lymph oma was observed in the thymus, with metastasis to the spleen and some lymp h nodes. However, there was no glomerulonephritis in 32 other mice bearing thymic lymphomas and in more than 40 males and females given MNU in the sam e study. Thus, the lesions in this mouse may have been spontaneous. Glomeru lonephritis was not found in more than 120 other male and female rasH2 mice in our facility. This is the first report of glomerulcnephritis in a rasH2 mouse, a promising candidate for medium-term carcinogenicity risk assessme nt.