title: Identification of quantitative trait loci for diabetic nephropathy in KK-Ay/Ta mice.
abstract: BACKGROUND
  The pathogenesis and development of human diabetic nephropathy involves genetic factors. Since human diabetic nephropathy is a heterogeneous disorder, identification of responsible gene loci is difficult. We studied candidate gene loci for diabetic nephropathy, using quantitative trait locus (QTL) analysis of a spontaneous animal model for diabetic nephropathy: KK-Ay/Ta × normal BALB/cA F2 intercross mice.
  
  
  METHODS
  We examined 270 (KK-Ay/Ta × BALB/cA) F2 intercross mice for their urinary albumin to creatinine ratios (ACRs), HbA1c and fasting body weights (FBW) at 8, 12, 16 and 20 weeks. Genotypes were investigated using 86 microsatellite markers with QTL analysis.
  
  
  RESULTS
  ACR in mice at 20 weeks and ACR gain showed a suggestive linkage to chromosome 9 (log of the odds [LOD] scores: 3.8 and 3.4, respectively; designated ACR-1). Gene loci contributing to HbA1c indicated a significant linkage to chromosome 7 (LOD: 5.8 and 8.9) in mice at 8 and 20 weeks (designated HbA1c-1), and FBW indicated a significant linkage to chromosome 1 (LOD: 5.5 and 5.2) in mice at 8 and 12 weeks (designated Fbw-1). At 20 weeks, glomerular to Bowman's capsule volume (G/B) ratio of F2 mice homozygous BB for D9Mit66 was significantly higher than that in homozygous KK and heterozygous KB F2 progeny. The sizes of pancreatic islets in F2 progeny homozygous KK and heterozygous KB for D7Mit100 were larger than those in homozygous BB F2 progeny.
  
  
  CONCLUSIONS
  QTL analysis of KK-Ay/Ta mice revealed several new loci contributing to diabetic nephropathy and related phenotypes. Thus, it appears that type 2 diabetes and nephropathy of KK-Ay/Ta mice have different genetic factors.
authors: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors: Tatsuya
authors: T
authors: Aoki
authors: Shigeru
authors: S
authors: Kaneko
authors: Mitsuo
authors: M
authors: Tanimoto
authors: Tomohito
authors: T
authors: Gohda
authors: Shinji
authors: S
authors: Hagiwara
authors: Maki
authors: M
authors: Murakoshi
authors: Yuji
authors: Y
authors: Ishikawa
authors: Masako
authors: M
authors: Furukawa
authors: Kazuhiko
authors: K
authors: Funabiki
authors: Satoshi
authors: S
authors: Horikoshi
authors: Yasuhiko
authors: Y
authors: Tomino
mesh_terms: D000419:Albuminuria / Q000235:genetics; D000483:Alleles; D000818:Animals; D001835:Body Weight / Q000235:genetics; D002874:Chromosome Mapping; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci
chemical_list: D003404:Creatinine; D006442:Glycated Hemoglobin