Journal Article

The inheritance of glomerulosclerosis in mice is controlled by multiple quantitative trait loci.

O Lenz, F Zheng, J Vilar, S Doublier, E Lupia, S Schwedler, L J Striker and G E Striker

in Nephrology Dialysis Transplantation

Volume 13, issue 12, pages 3074-3078
Published in print December 1998 | ISSN: 0931-0509
Published online December 1998 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/13.12.3074
The inheritance of glomerulosclerosis in mice is controlled by multiple quantitative trait loci.

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BACKGROUND: Glomerulosclerosis, the common terminal event in chronic glomerular diseases such as diabetic nephropathy or IgA nephropathy, leads to end-stage renal disease. The considerable variation in both the risk of developing glomerulosclerosis and the rate of progression in individual patients suggest a role for genetic factors which have not been identified so far. In this study we sought to examine the mode of inheritance of glomerulosclerosis in mice. METHODS: F1 animals of a mating between glomerulosclerosis-prone ROP-Os/+ male and non-sclerotic C3H female mice were backcrossed to the ROP strain. We took advantage of the radiation-induced mutation oligosyndactylism (Os) to identify glomerulosclerosis at the age of 3 months. Kidneys were perfused in situ with PBS/Formalin 10%. The extent of glomerulosclerotic lesions was evaluated on PAS stained paraffin sections using computer-aided morphometry. RESULTS: F1 mice did not show any glomerulosclerosis. In the backcross offspring, we found a wide distribution of glomerular lesions between individual animals, ranging from normal to very severe. We calculated that at least 8-10 loci determine the severity of glomerulosclerosis in mice. CONCLUSIONS: Our data show that glomerulosclerosis is inherited in a recessive fashion involving at least 8-10 loci.

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Subjects: Nephrology

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