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M. C. Lai, N. Binz, J. A. Eade, M. de Pinho, R. P. Himbeck, E. P. Rakoczy; Characterization of the Akimba Mouse: A Diabetic Mouse With Ocular and Renal Changes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3996. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To generate and characterize a diabetic mouse with retinopathic and nephropathic changes
All animal experimentation was conducted in compliance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. The Ins2C96Y Akita mouse (model for diabetes) was mated with the Kimba mouse [model of vascular endothelial growth factor (VEGF)-driven retinal neovascularization]. Male offspring with the Kimba and Akita genotypes (Akimba mouse) were subjected to routine physical, biochemical (blood glucose measurement) and clinical [color fundus photography (CFP), fundus fluorescein angiography (FFA)] examinations. Mice were sacrificed at different ages and their eyes and kidneys were processed for histology. Male non-Akimba littermates, i.e. mice with Akita, Kimba or background (C57Bl/6) genotypes were used as comparison and as control, respectively.
Akimba mice have elevated blood glucose levels from 4 weeks postnatal (>25mmol/L) and exhibited the diabetic phenotype described for the Akita parent strain. CFP and FFA demonstrated neovascular pathologies such as microaneurysms, capillary drop-out and increased vessel permeability which were similar to the Kimba mouse. Preliminary analysis showed a more severe loss of photoreceptors in the Akimba mice compared to the Kimba mice, suggesting that hyperglycaemia may exacerbate progression of retinopathy. Decrease in body weight with age was comparable to the Akita parent. At autopsy, loss of body fat and presence of significantly enlarged kidneys were evident in the Akimba and Akita mice. In addition, hydronephrosis and marked mesangial expansion with presence of Armanni-Epstein bodies were observed in Akita and Akimba mouse kidneys.
Our data suggest that the Akimba mouse is a good model for diabetes-related complications such as retinopathy and nephropathy. It may provide a very powerful resource for understanding the individual and combined effects of VEGF upregulation and hyperglycemia in eyes and kidneys.
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