» Articles » PMID: 15965785

Quantitative Trait Loci for Proteinuria in the Focal Glomerulosclerosis Mouse Model

Overview
Journal Mamm Genome
Specialty Genetics
Date 2005 Jun 21
PMID 15965785
Citations 3
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

A major X-linked locus affects kidney function in mice.

Leduc M, Savage H, Stearns T, Cario C, Walsh K, Paigen B Mol Genet Genomics. 2012; 287(11-12):845-54.

PMID: 23011808 PMC: 3508201. DOI: 10.1007/s00438-012-0720-x.


Genetic analysis of albuminuria in aging mice and concordance with loci for human diabetic nephropathy found in a genome-wide association scan.

Tsaih S, Pezzolesi M, Yuan R, Warram J, Krolewski A, Korstanje R Kidney Int. 2009; 77(3):201-10.

PMID: 19924099 PMC: 2807478. DOI: 10.1038/ki.2009.434.


Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains.

Wilson K, McIndoe R, Eckenrode S, Morel L, Agarwal A, Croker B BMC Nephrol. 2005; 6:17.

PMID: 16371158 PMC: 1334202. DOI: 10.1186/1471-2369-6-17.

References
1.
Yoshida F, Matsuo S, Fujishima H, Kim H, Tomita T . Renal lesions of the FGS strain of mice: a spontaneous animal model of progressive glomerulosclerosis. Nephron. 1994; 66(3):317-25. DOI: 10.1159/000187830. View

2.
Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A . NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet. 2000; 24(4):349-54. DOI: 10.1038/74166. View

3.
Manly K, Cudmore Jr R, Meer J . Map Manager QTX, cross-platform software for genetic mapping. Mamm Genome. 2001; 12(12):930-2. DOI: 10.1007/s00335-001-1016-3. View

4.
Sharma M, Sharma R, McCarthy E, Savin V . "The FSGS factor:" enrichment and in vivo effect of activity from focal segmental glomerulosclerosis plasma. J Am Soc Nephrol. 1999; 10(3):552-61. DOI: 10.1681/ASN.V103552. View

5.
Brown D, Provoost A, Daly M, Lander E, Jacob H . Renal disease susceptibility and hypertension are under independent genetic control in the fawn-hooded rat. Nat Genet. 1996; 12(1):44-51. DOI: 10.1038/ng0196-44. View