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537129 
Journal Article 
Genetic dissection of proteinuria in the Sabra rat 
Yagil, C; Sapojnikov, M; Wechsler, A; Korol, A; Yagil, Y 
2006 
1 
Physiological Genomics
ISSN: 1094-8341
EISSN: 1531-2267 
25 
1 
121-133 
English 
16390874 
WOS:000236722700013 
The pathophysiology underlying proteinuria remains incompletely understood and warrants further research. We currently initiated the investigation of the genetic basis of proteinuria in the Sabra rat, a model of salt susceptibility that we showed previously to be also a model of spontaneous proteinuria that is unrelated to salt loading or development of hypertension. We applied the total genome scan strategy in 75 F-2 male animals derived from a cross between SBH/y, which are prone to develop proteinuria, and SBN/y, which are relatively resistant to the development of proteinuria. Animals were subjected to uninephrectomy (UNx) to accelerate the development of proteinuria and were provided chow with a low salt content, thus avoiding the development of hypertension. Urinary protein excretion was monitored before UNx and monthly thereafter for 8 mo. The genotype of F-2 was determined with microsatellite markers. The data were analyzed for cosegregation by ANOVA and for genetic linkage with a novel multifaceted statistical genetic paradigm. We detected three proteinuria-related quantitative trait loci (QTL) that were associated with the salt sensitivity (H) alleles from SBH/y: SUP2, SUP17, and SUP20 on rat chromosomes (Chr) 2, 17, and 20. We detected an additional QTL on Chr 3, SUP3, that was associated with the salt resistance (N) alleles from SBN/y. A temporal effect was noted: QTL SUP2 and SUP17 surfaced at months 7 - 8, QTL SUP20 at months 6 - 8, and QTL SUP3 at months 5 - 6. The QTL emerging from this study lead us a step closer to identifying the genes associated with and elucidating the pathophysiology of proteinuria. 
SBH/y; SBN/y; linkage analysis; quantitative trait locus; quantitative trait loci; early-onset albuminuria; salt-sensitive rats; renal damage; mapping analysis; dahl rats; hypertension; susceptibility; model; linkage