title: Quantitative trait loci for proteinuria in the focal glomerulosclerosis mouse model.
abstract: The FGS/Kist strain of mice, a new animal model for focal glomerulosclerosis (FGS) in humans, was previously established by recurrent selection for high proteinuria, which is a principal marker of FGS, from descendants of CBA/Nga and RFM/Nga strains. We performed a genome-wide scan for quantitative trait loci (QTLs) affecting proteinuria in a population of 356 backcross progeny derived from a cross between FGS/Kist and the standard normal strain, C57BL/6J. Five proteinuria QTLs (Ptnu1-5) were detected at the genome-wide 5% or less level. Ptnu1 and Ptnu2, located on Chromosomes (Chrs) 8 and 17, respectively, had main effects on proteinuria and also interacted epistatically with each other. However, Ptnu3 on Chr 9 and Ptnu4 and Ptnu5 both on Chr 15 had epistatic interaction effects only. Except for the epistatic interaction effect of Ptnu4 and Ptnu5, all alleles derived from FGS/Kist were responsible for the high proteinuria. These results indicated that the genetic control of proteinuria is complex and the identified QTLs may provide new insights into the pathogenesis of FGS in mice as well as in humans.
authors.affiliation: Laboratory of Animal Genetics, Division of Applied Genetics and Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Byung-Hwa
authors.initials: BH
authors.lastname: Hyun
authors.forename: Jun-Gyo
authors.initials: JG
authors.lastname: Suh
authors.forename: Yang-Seok
authors.initials: YS
authors.lastname: Oh
authors.forename: Takao
authors.initials: T
authors.lastname: Namikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Ishikawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D004843:Epistasis, Genetic; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications*; D051379:Mice; D008817:Mice, Mutant Strains; D011507:Proteinuria / Q000209:etiology / Q000235:genetics*; D040641:Quantitative Trait Loci