title: Mapping quantitative trait loci for proteinuria-induced renal collagen deposition.
abstract: The progression of chronic kidney disease is a complex process influenced by genetic factors. Proteinuria is a predictor of functional deterioration and an accelerator of disease progression through renal parenchymal damage and interstitial fibrosis. To determine genetic components that might mediate renal fibrosis due to proteinuria, we mapped loci influencing the phenotype of two mouse strains differing in proteinuria-induced renal type I collagen (COLI) deposition. Collagen I deposition in 129S1/svImJ and C57BL/6J mice differs significantly among tested strains. We backcrossed 120 hemi-nephrectomized (129S1/svImJ x C57BL/6J) F1 x 129S1/svImJ backcrossed mice loaded with bovine serum albumin giving rise to proteinuria and renal COLI deposition. Quantitative trait loci (QTL) mapping was performed and our analysis identified one suggestive linkage for renal COLI deposition peaking at 87 cM near D2Mit224 (logarithm of odds: 2.41) on Chr 2. In silico analysis uncovered nine candidate genes. Hence, although more studies are needed, these QTL provide an initial cue to subsequent gene discovery, which might help unravel the genetics of renal fibrosis.
authors.affiliation: Department of Nephrology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Kanno
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Okada
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D011507:Proteinuria / Q000235:genetics* / Q000378:metabolism*; D040641:Quantitative Trait Loci
chemical_list: D024042:Collagen Type I