title: Glomerular changes in the KK-Ay/Ta mouse: a possible model for human type 2 diabetic nephropathy.
abstract: BACKGROUND
  In type 2 diabetic nephropathy, there is no animal model which has been completely matched with humans. Advanced glycation end products (AGE) and transforming growth factor-beta (TGF-beta) are closely related to hyperglycaemia and their pathobiochemistry could explain diabetic nephropathy. The objective of the present study was to evaluate the KK-A(y)/Ta mouse as a suitable model for type 2 diabetic nephropathy including pathological changes and immunohistochemical analyses of AGE and TGF-beta, compared with the non-diabetic BALB/cA mouse.
  
  
  METHODS
  The urinary albumin/creatinine ratio (ACR), body weight (BW), fasting and casual blood glucose, blood haemoglobin A(1c) (HbA(1c)), creatinine clearance (Ccr) and blood pressure were measured for phenotypic characterisation. The pathological changes of glomeruli were evaluated by light microscopy, immunofluorescence and electron microscopy. AGE and TGF-beta accumulation were evaluated by immunoperoxidase staining.
  
  
  RESULTS
  The mean levels of ACR, casual blood glucose, blood HbA(1c) and Ccr in KK-A(y)/Ta mice were higher than those in age-matched non-diabetic BALB/cA mice after 12 weeks of age. There were no significant changes in the levels of systemic blood pressure among all groups. The pathological changes of glomeruli in KK-A(y)/Ta mice were consistent with those in the early stage of human diabetic nephropathy. AGE and TGF-beta protein appeared to be localised in the glomerular mesangial matrices.
  
  
  CONCLUSIONS
  It appears that KK-A(y)/Ta mice, especially in terms of histopathological findings, are a suitable animal model for the early stage of type 2 diabetic nephropathy.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ito
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Kaori
authors.initials: K
authors.lastname: Yamada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kaneko
authors.forename: Masakazu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Obayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Maki
authors.initials: M
authors.lastname: Murakoshi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aoki
authors.forename: Michiro
authors.initials: M
authors.lastname: Wakabayashi
authors.forename: Tomohito
authors.initials: T
authors.lastname: Gohda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Funabiki
authors.forename: Kunimi
authors.initials: K
authors.lastname: Maeda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000032:analysis; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D017127:Glycation End Products, Advanced; D016212:Transforming Growth Factor beta