The inheritance of glomerulosclerosis in mice is controlled by multiple quantitative trait loci.
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.
Lenz
O
O
Renal Cell Biology Section, Metabolic Diseases Branch, NIDDK, NIH, Bethesda, MD, USA.
Zheng
F
F
Vilar
J
J
Doublier
S
S
Lupia
E
E
Schwedler
S
S
Striker
L J
LJ
Striker
G E
GE
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D005808:Genes, Recessive / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology; D006824:Hybridization, Genetic; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains / Q000235:genetics; D019655:Quantitative Trait, Heritable