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

Background. Glomerulosclerosis, the common terminal event in chronic glomer ular diseases such as diabetic nephropathy or IgA nephropathy, leads to end -stage renal disease. The considerable variation in both the risk of develo ping glomerulosclerosis and the rate of progression in individual patients suggest a role for genetic factors which have not been identified so far. I n this study we sought to examine the mode of inheritance of glomeruloscler osis in mice. Methods. F1 animals of a mating between glomerulosclerosis-prone ROP-Os/+ m ale and non-sclerotic C3H female mice were backcrossed to the ROP strain. W e took advantage of the radiation-induced mutation oligosyndactylism (Os) t o identify glomerulosclerosis at the age of 3 months. Kidneys were perfused in situ with PBS/Formalin 10%. The extent of glomerulosclerotic lesions wa s evaluated on PAS stained paraffin sections using computer-aided morphomet ry. Results. F1 mice did not show any glomerulosclerosis. In the backcross offs pring, we found a wide distribution of glomerular lesions between individua l 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 recess ive fashion involving at least 8-10 loci.