title: The inheritance of glomerulosclerosis in mice is controlled by multiple quantitative trait loci.
abstract: 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.
authors.affiliation: Renal Cell Biology Section, Metabolic Diseases Branch, NIDDK, NIH, Bethesda, MD, USA.
authors.forename: O
authors.initials: O
authors.lastname: Lenz
authors.forename: F
authors.initials: F
authors.lastname: Zheng
authors.forename: J
authors.initials: J
authors.lastname: Vilar
authors.forename: S
authors.initials: S
authors.lastname: Doublier
authors.forename: E
authors.initials: E
authors.lastname: Lupia
authors.forename: S
authors.initials: S
authors.lastname: Schwedler
authors.forename: L J
authors.initials: LJ
authors.lastname: Striker
authors.forename: G E
authors.initials: GE
authors.lastname: Striker
mesh_terms: 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