Characterization of Diabetic Nephropathy in a Transgenic Model of Nonobese
Authors Yukiko Kanetsuna, Keita Hirano, Michio Nagata, Maureen A Gannon, Raymond C.
Harris, Matthew D. Breyer, and Takamune Takahashi
Submitted By Matthew Breyer on 9/6/2005
Status Published
Journal American journal of physiology. Renal physiology
Year 2006
Date Published 12/1/2006
Volume : Pages 291(6) : F1315 - F1322
PubMed Reference 16705146
Abstract Genetic mouse models provide a unique opportunity to investigate gene
function in the natural course of the disease. Although diabetic
nephropathy (DN) in models of type II diabetes has been well
characterized, diabetic renal disease in nonobese diabetic mice is
still incompletely understood. Here, we characterized renal changes
in the pdx1PB-HNF6 transgenic mouse that exhibits β-cell dysfunction
and nonobese diabetes. Male transgenics developed hyperglycemia by
the age of 7 weeks and survived over a year without insulin
treatment. Diabetes ensued earlier and progressed more severely in
the HNF6 males than the females. The HNF6 males exhibited albuminuria
as early as 10 weeks of age and the urinary albumin excretion
increased with age, exceeding 150 µg/24 h at 11 months of age.
Diabetic males developed renal hypertrophy after 7 weeks of age,
whereas glomerular hyperfiltration was not observed in the mice.
Hypertension and hyperlipidemia were not observed in the diabetic
mice. Histological analysis of the HNF6 kidneys displayed diabetic
glomerular changes, including glomerular enlargement, diffuse
mesangial proliferation and matrix expansion, thickened glomerular
basement membrane and arteriolar hyalinosis. Mesangial matrix
accumulation increased with age, resulting in nodular lesions by 44
weeks of age. Immunohistochemistry showed accumulation of type IV
collagen and TGFβ1 in the mesangial area. No significant immune
complex deposition was observed in the HNF6 glomeruli. Thus, the HNF6
mouse exhibits diabetic renal changes that parallel the early phase
of human DN. The model should facilitate studies of genetic and
environmental factors that may affect DN in nonobese diabetes.


Onecut1one cut domain, family member 1
Tgfb1transforming growth factor, beta 1