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A model for diabetic nephropathy: Advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin‐induced diabetic mouse
Author(s) -
Inada Akari,
Kanamori Hiroshi,
Arai Hidenori,
Akashi Tomoyuki,
Araki Makoto,
Weir Gordon C.,
Fukatsu Atsushi
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21316
Subject(s) - streptozotocin , diabetic nephropathy , medicine , endocrinology , renal hypertrophy , diabetes mellitus , kidney , insulin , genetically modified mouse , toxicity , transgene , biology , biochemistry , gene
We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER Iγ) transgenic (Tg) mice. The ICER Iγ Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin‐producing β cells. Here in a longitudinal study we further analyzed diabetic nephropathy and structural and functional alterations in other organs, comparing our model with streptozotocin (STZ)‐diabetic model mice. The high‐dose STZ‐diabetic model showed marked variation in blood glucose levels and severe toxicity of STZ in the liver and kidney. The low‐dose STZ‐diabetic model showed less toxicity, but the survival rate was very low. STZ‐diabetic mice had much more variation of glomerular hypertrophy and sclerosis. Furthermore, non‐specific toxicity of STZ or insulin injections to maintain optimal blood glucose levels might have another effect upon the diabetic renal changes. In contrast, ICER Iγ Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER Iγ Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model. J. Cell. Physiol. 215: 383–391, 2008. © 2008 Wiley‐Liss, Inc.