title: Genetic dissection of proteinuria in the Sabra rat.
abstract: 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 F2 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 F2 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.
authors.affiliation: Laboratory for Molecular Medicine, Israeli Rat Genome Center, Faculty of Health Sciences, Ben-Gurion University, Barzilai Medical Center Campus, Ashkelon, Israel.
authors.forename: Chana
authors.initials: C
authors.lastname: Yagil
authors.forename: Marina
authors.initials: M
authors.lastname: Sapojnikov
authors.forename: Alexander
authors.initials: A
authors.lastname: Wechsler
authors.forename: Abraham
authors.initials: A
authors.lastname: Korol
authors.forename: Yoram
authors.initials: Y
authors.lastname: Yagil
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D008040:Genetic Linkage; D005838:Genotype; D008126:Lod Score; D008297:Male; D023421:Models, Animal; D011506:Proteins / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics*; D040641:Quantitative Trait Loci; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D011506:Proteins