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J. Makita, J. Randazzo, K. Blessing, J.-Y. Tsai, P. F. Kador; Novel Diabetic Mouse Models for Investigating Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1343.
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Although mice are an attractive animal model for investigating long-term diabetic complications, retinal biochemical changes in streptozotocin diabetic mice differ from those in streptozotocin-diabetic rats. Differences in retinal oxidative changes in mice versus rats have been suggested to be linked to lower levels of aldose reductase (AR) in the mouse. The purpose of this study was to develop a naturally diabetic mouse with increased levels of retinal aldose whose retinal vasculature can be easily differentiated.
Transgenic C57BL mice expressing either green fluorescent protein (SMAA-GFP) or human AR (SMAA-hAR) in vascular cells expressing smooth muscle actin were crossbred to develop a new colony expressing both attributes (SMAA-GFP-hAR). Subsequently the SMAA-GFP and SMAA-GFP-hAR mice were crossbred with male heterozygous C57BL/6-Ins2Akita/J mice. All offspring were genotyped using DNA preparations from tail snips amplified by PCR and then analyzed by agarose gel electrophoresis. Retinal and lens sorbitol levels in these mice were determined by HPLC.
Genotyping confirmed that > 95% of all offspring from the SMAA-GFP, SMAA-hAR, and SMAA-GFP-hAR colonies demonstrate their respective traits. Breeding male heterozygous C57BL/6-Ins2Akita/J mice with transgenics possessing the hAR and GFP traits resulted in viable offspring possessing all desired traits. Blood glucose measurements at 8 weeks of age confirmed that these Akita transgenics were diabetic, with males demonstrating significant higher average blood glucose levels (553 mg/dL) compared to females (325 mg/dL). Sorbitol levels in isolated neural retinas were 35% higher in C57BL/6-Ins2Akita/J-SMAA-GFP-hAR mice compared to C57BL/6-Ins2Akita/J-SMAA-GFP mice.
These new mouse models of early onset diabetes are valuable tools for addressing the relationship between hyperglycemia, pericyte degeneration, AR and the onset of other retinal vascular lesions.
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