title: Quantitative trait Loci for resistance to the congenital nephropathy in tensin 2-deficient mice.
abstract: The ICR-derived glomerulonephritis (ICGN) mouse is a chronic kidney disease (CKD) model that is characterized histologically by glomerulosclerosis, vascular sclerosis and tubulointerstitial fibrosis, and clinically by proteinuria and anemia, which are common symptoms and pathological changes associated with a variety of kidney diseases. Previously, we performed a quantitative trait locus (QTL) analysis to identify the causative genes for proteinuria in ICGN mice, and found a deletion mutation of the tensin 2 gene (Tns2nph, MGI no: 2447990). Interestingly, the congenic strain carrying the Tns2nph mutation on a C57BL/6J (B6) genetic background exhibited milder phenotypes than did ICGN mice, indicating the presence of several modifier genes controlling the disease phenotype. In this study, to identify the modifier/resistant loci for CKD progression in Tns2-deficient mice, we performed QTL analysis using backcross progenies from susceptible ICGN and resistant B6 mice. We identified a significant locus on chromosome (Chr) 2 (LOD = 5.36; 31 cM) and two suggestive loci on Chrs 10 (LOD = 2.27; 64 cM) and X (LOD = 2.65; 67 cM) with linkage to the severity of tubulointerstitial injury. One significant locus on Chr 13 (LOD = 3.49; approximately 14 cM) and one suggestive locus on Chr 2 (LOD = 2.41; 51 cM) were identified as QTLs for the severity of glomerulosclerosis. Suggestive locus in BUN was also detected in the same Chr 2 region (LOD = 2.34; 51 cM). A locus on Chr 2 (36 cM) was significantly linked with HGB (LOD = 4.47) and HCT (LOD = 3.58). Four novel epistatic loci controlling either HGB or tubulointerstitial injury were discovered. Further genetic analysis should lead to identification of CKD modifier gene(s), aiding early diagnosis and providing novel approaches to the discovery of drugs for the treatment and possible prevention of kidney disease.
authors: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors: Hayato
authors: H
authors: Sasaki
authors: Laboratory of Laboratory Animal Science and Medicine, Faculty of Veterinary Medicine, Kitasato University, Towada, Japan.
authors: Nobuya
authors: N
authors: Sasaki
authors: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors: Tomohiro
authors: T
authors: Nishino
authors: Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan.
authors: Ken-Ichi
authors: K
authors: Nagasaki
authors: Department of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors: Hiroshi
authors: H
authors: Kitamura
authors: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors: Daisuke
authors: D
authors: Torigoe
authors: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors: Takashi
authors: T
authors: Agui
mesh_terms: D000818:Animals; D060045:Genes, Modifier; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics*; D040641:Quantitative Trait Loci; D000070876:Tensins
chemical_list: D000070876:Tensins; D010749:Phosphoprotein Phosphatases; C511707:Tns2 protein, mouse