Glomerular changes in the KK-Ay/Ta mouse: a possible model for human type 2 diabetic nephropathy.
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.
Ito
Takamichi
T
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Tanimoto
Mitsuo
M
Yamada
Kaori
K
Kaneko
Shigeru
S
Matsumoto
Masakazu
M
Obayashi
Keiko
K
Hagiwara
Shinji
S
Murakoshi
Maki
M
Aoki
Tatsuya
T
Wakabayashi
Michiro
M
Gohda
Tomohito
T
Funabiki
Kazuhiko
K
Maeda
Kunimi
K
Horikoshi
Satoshi
S
Tomino
Yasuhiko
Y
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
D017127:Glycation End Products, Advanced; D016212:Transforming Growth Factor beta