title: Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits.
abstract: Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUC-Lepr (faSte) (ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-(D1Rat42-D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation (Lepr (faSte)) (P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC Lepr (faSte). Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function.
authors.affiliation: Department of Pediatrics, University of California, Davis, California 95616, USA. chwarden@ucdavis.edu
authors.forename: Craig H
authors.initials: CH
authors.lastname: Warden
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Gularte-Mérida
authors.forename: Janis S
authors.initials: JS
authors.lastname: Fisler
authors.forename: Susan
authors.initials: S
authors.lastname: Hansen
authors.forename: Noreene
authors.initials: N
authors.lastname: Shibata
authors.forename: Anh
authors.initials: A
authors.lastname: Le
authors.forename: Juan F
authors.initials: JF
authors.lastname: Medrano
authors.forename: Judith S
authors.initials: JS
authors.lastname: Stern
mesh_terms: D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D008040:Genetic Linkage; D005838:Genotype; D007674:Kidney Diseases / Q000235:genetics / Q000662:veterinary; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011924:Rats, Zucker; D054411:Receptors, Leptin / Q000235:genetics*
chemical_list: D054411:Receptors, Leptin