Characterization of susceptibility of inbred mouse strains to diabetic nephropathy
Characterization of susceptibility of inbred mouse strains to diabetic nephropathy
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DOI：
10.2337/diabetes.54.9.2628
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发表时间：
2005-09-01
期刊：
影响因子：
7.7
通讯作者：
Breyer, MD
中科院分区：
文献类型：
--
作者：
Qi, ZH;Fujita, H;Breyer, MD
已在人类中观察到对糖尿病肾病的不同易感性，但在近交系小鼠中尚未得到明确定义。目前的研究描述了六种近交小鼠品系的糖尿病肾病的严重程度，包括 C57BL/6J、DBA/2J、FVB/NJ、MRL/MpJ、A/J 和 KK/HIJ 小鼠。使用低剂量链脲佐菌素注射诱发糖尿病。通过连续测量尿白蛋白排泄量、肾小球滤过率 (GFR) 和 25 周内肾脏形态的最终评估来评估肾损伤的进展。尽管高血糖水平相当，但菌株之间的尿白蛋白排泄和肾脏组织病理学变化却显着不同。 DBA/2J 和 KK/HIJ 小鼠比 C57BL/6J、MRL/MpJ 和 A/J 小鼠出现明显更多的蛋白尿。在糖尿病 DBA/2J 和 KK/HIJ 小鼠中观察到严重的肾小球系膜扩张、结节性肾小球硬化和小动脉透明变性。除 A/J 外，所有研究的糖尿病菌株均观察到肾小球过度滤过。在 25 周的研究期间，GFR 的显着下降并不明显，但糖尿病 DBA/2J 小鼠表现出 GFR 下降的趋势。综上所述，这些结果表明近交小鼠对糖尿病肾病的易感性存在差异。 DBA/2J和KK/H1J小鼠更容易患糖尿病肾病，而最广泛使用的C57BL/6J小鼠相对不易发展为糖尿病肾病。
Differential susceptibility to diabetic nephropathy has been observed in humans, but it has not been well defined in inbred strains of mice. The present studies characterized the severity of diabetic nephropathy in six inbred mouse strains including C57BL/6J, DBA/2J, FVB/NJ, MRL/MpJ, A/J, and KK/HIJ mice. Diabetes mellitus was induced using low-dose streptozotocin injection. Progression of renal injury was evaluated by serial measurements of urinary albumin excretion, glomerular filtration rate (GFR), and terminal assessment of renal morphology over 25 weeks. Despite comparable levels of hyperglycemia, urinary albumin excretion and renal histopathological changes were dramatically different among strains. DBA/2J and KK/HIJ mice developed significantly more albuminuria than C57BL/6J, MRL/MpJ, and A/J mice. Severe glomerular mesangial expansion, nodular glomerulosclerosis, and arteriolar hyalinosis were observed in diabetic DBA/2J and KK/HIJ mice. Glomerular hyperfiltration was observed in all diabetic strains studied except A/J. The significant decline in GFR was not evident over the 25-week period of study, but diabetic DBA/2J mice exhibited a tendency for GFR to decline. Taken together, these results indicate that differential susceptibility to diabetic nephropathy exists in inbred mice. DBA/2J and KK/HlJ mice are more prone to diabetic nephropathy, whereas the most widely used C57BL/6J mice are relatively resistant to development of diabetic nephropathy.