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Pathogenesis and treatment of type 2 diabetic nephropathy: lessons from the spontaneous KK/Ta mouse model

Yasuhiko Tomino1, Mitsuo Tanimoto, Toshihide Shike

  • 1Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan. yasu@med.juntendo.ac.jp

Current Diabetes Reviews
|January 29, 2008
PubMed

Insights

The KK/Ta mouse model offers a valuable tool for studying diabetic nephropathy, closely mimicking human early-stage kidney disease. This model aids research into genetic factors and treatments for type 2 diabetes complications.

Area of Science:

  • Nephrology
  • Endocrinology
  • Genetics

Background:

  • Diabetic nephropathy is a leading cause of end-stage renal failure in diabetes patients.
  • Disease progression is influenced by genetic, hyperglycemic, hypertensive, and dyslipidemic factors.
  • Human diabetic nephropathy is complex, necessitating reliable animal models for mechanistic studies.

Purpose of the Study:

  • To evaluate the KK/Ta mouse as a model for human type 2 diabetes and early diabetic nephropathy.
  • To review genetic susceptibility factors using genome-wide linkage analysis and DD-PCR/Northern blot.
  • To examine the efficacy of treatments like ARBs and TZDs in this model.

Main Methods:

  • Comparative analysis of KK/Ta mice and BALB/c mice for metabolic and renal parameters.
  • Genome-wide linkage analysis to identify genetic susceptibility loci.
  • Differential display polymerase chain reaction (DD-PCR) and Northern blot analysis for gene expression.
  • Administration of angiotensin type 1 (AT1) receptor blockers (ARBs) and thiazolidinediones (TZDs) to assess treatment effects.

Main Results:

  • KK/Ta mice exhibit distinct genetic backgrounds, body weight, blood glucose, impaired glucose tolerance, albuminuria, and triglyceride levels compared to BALB/c mice.
  • Renal lesions in KK/Ta mice closely resemble early human diabetic nephropathy.
  • The KK/Ta model is suitable for investigating genetic factors and therapeutic interventions in diabetic nephropathy.

Conclusions:

  • The KK/Ta mouse is a relevant model for studying type 2 diabetes and early diabetic nephropathy.
  • This model facilitates the investigation of genetic susceptibility and the evaluation of potential treatments for diabetic kidney disease.

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