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Localization of genetic loci controlling hydronephrosis in the Brown Norway rat and its association with hematuria

Item Type:Article
Title:Localization of genetic loci controlling hydronephrosis in the Brown Norway rat and its association with hematuria
Creators Name:Kota, L.T., Schulz, H., Falak, S., Huebner, N. and Osborne-Pellegrin, M.
Abstract:The aim of this study was to investigate the genetic basis of congenital hydronephrosis (HN), a poorly defined pathological entity, using a rat model. The Brown Norway (BN) strain presents spontaneously a high incidence of apparently asymptomatic HN, whereas the LOU strain does not. A backcross was established between these two strains [BNx(BNxLOU)] and a genome-wide scan performed with 193 microsatellite markers on 121 males and 118 females of this population, which had been phenotyped and scored for HN severity (defined as the degree of renal pelvic dilation), followed by linkage analysis using Mapmaker/QTL software. Bilateral HN score was significantly linked to a locus on chromosome 6 (Z-scores 4.4 and 4.8 for all rats and for females respectively). Suggestive loci were identified on chromosomes 2 (for only right-sided HN) and 4. This is the first study in rat to identify genetic loci for HN. 3 candidate genes present in these loci were sequenced and insertions detected in Id2 and Agtr1b genes in BN, which did not however lead to modified expression as measured by quantitative PCR. Production of a congenic line for part of the chromosome 6 locus confirmed its involvement in HN, but the phenotype was mild. Evidence of hematuria was observed in 9.6% of the backcross rats, mostly males and only in kidneys with HN, but not necessarily in the most severely affected. Hematuria also occurs in the BN colony used here, where it is due to papilloma-like lesions involving pelvic epithelial proliferation, but not in the LOU.
Keywords:LOU Rat, Quantitative Trait Loci, Congenic Line, Renal Pelvic Epithelial Proliferation, Animals, Rats
Source:Physiological Genomics
Publisher:American Physiological Society
Page Range:215-224
Date:15 July 2008
Official Publication:https://doi.org/10.1152/physiolgenomics.00221.2007
PubMed:View item in PubMed

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