title: A model for diabetic nephropathy: advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin-induced diabetic mouse.
abstract: We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER Igamma) transgenic (Tg) mice. The ICER Igamma Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin-producing beta 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 Igamma Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER Igamma Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model.
authors.affiliation: SSP Stem Cell Unit, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Inada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanamori
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Araki
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukatsu
mesh_terms: D000818:Animals; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000209:etiology; D007515:Islets of Langerhans / Q000473:pathology; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013311:Streptozocin / Q000009:adverse effects
chemical_list: D051786:Cyclic AMP Response Element Modulator; D013311:Streptozocin